| Citation: | Wen-Kai Yu, Qing-Ru Zhu, Li Zhou, Xin-Lei Shen, Tian-Yang Cheng, Yi-Ni Bao, Gang Cao. Small molecules targeting regulated cell death for chronic kidney disease therapy[J]. Journal of Pharmaceutical Analysis. doi: 10.1016/j.jpha.2025.101427
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Chronic kidney disease (CKD) is a significant contributor to the global morbidity of non-communicable diseases and is predicted to become the fifth leading cause of death worldwide. However, effective treatments that directly target the underlying causes of CKD remain limited due to its complicated pathogenesis. Recent research has increasingly focused on elucidating the molecular mechanisms and identifying new therapeutic targets of CKD. In recent years, regulated cell death (RCD) has been highlighted as a central mechanism in the development and progression of CKD, suggesting that targeting specific RCD signaling pathways may offer effective strategies for CKD. Emerging research reveals that small molecules can effectively target different types of RCD in the context of CKD, including apoptosis, autophagy-dependent cell death, pyroptosis, ferroptosis and necroptosis. In this review, we summarize current understanding of the mechanism of RCD in CKD. Importantly, we emphasize the regulatory mechanism of small molecules on disturbed RCD to alleviate CKD. Taken together, this review enhances the comprehension of small molecules as modulators of RCD against CKD, which will provide new insights and potential avenues for CKD therapy.
| [1] |
K.J. Foreman, N. Marquez, A. Dolgert, et al., Forecasting life expectancy, years of life lost, and all-cause and cause-specific mortality for 250 causes of death: Reference and alternative scenarios for 2016-40 for 195 countries and territories, Lancet 392 (2018) 2052-2090.
|
| [2] |
H.J. Anders, T.B. Huber, B. Isermann, et al., CKD in diabetes: Diabetic kidney disease versus nondiabetic kidney disease, Nat. Rev. Nephrol. 14 (2018) 361-377.
|
| [3] |
J.P. Borges, R.S.R. Saetra, A. Volchuk, et al., Glycine inhibits NINJ1 membrane clustering to suppress plasma membrane rupture in cell death, Elife 11 (2022), e78609.
|
| [4] |
L. Galluzzi, I. Vitale, S.A. Aaronson, et al., Molecular mechanisms of cell death: Recommendations of the Nomenclature Committee on Cell Death 2018, Cell Death Differ. 25 (2018) 486-541.
|
| [5] |
A.C. Webster, E.V. Nagler, R.L. Morton, et al., Chronic kidney disease, Lancet 389 (2017) 1238-1252.
|
| [6] |
J. Chen, H. Li, Y. Bai, et al., Spatially resolved multi-omics unravels region-specific responses, microenvironment remodeling and metabolic reprogramming in aristolochic acid nephropathy, Innov. Med. 2 (2024), 100066.
|
| [7] |
A.B. Sanz, M.D. Sanchez-Nino, A.M. Ramos, et al., Regulated cell death pathways in kidney disease, Nat. Rev. Nephrol. 19 (2023) 281-299.
|
| [8] |
T. Xie, L. Yao, X. Li, Advance in iron metabolism, oxidative stress and cellular dysfunction in experimental and human kidney diseases, Antioxidants 13 (2024), 659.
|
| [9] |
Y. Ai, Y. Meng, B. Yan, et al., The biochemical pathways of apoptotic, necroptotic, pyroptotic, and ferroptotic cell death, Mol. Cell 84 (2024) 170-179.
|
| [10] |
A. Belavgeni, C. Meyer, J. Stumpf, et al., Ferroptosis and necroptosis in the kidney, Cell Chem. Biol. 27 (2020) 448-462.
|
| [11] |
E. Mishima, T. Nakamura, S. Doll, et al., Recommendations for robust and reproducible research on ferroptosis, Nat. Rev. Mol. Cell Biol. (2025).
|
| [12] |
M. Tajaldini, A. Poorkhani, T. Amiriani, et al., Strategy of targeting the tumor microenvironment via inhibition of fibroblast/fibrosis remodeling new era to cancer chemo-immunotherapy resistance, Eur. J. Pharmacol. 957 (2023), 175991.
|
| [13] |
S. Dhillon, Daprodustat: First approval, Drugs 80 (2020) 1491-1497.
|
| [14] |
X. Hu, W. Zhao, J. Deng, et al., Mangiferin alleviates renal inflammatory injury in spontaneously hypertensive rats by inhibiting MCP-1/CCR2 signaling pathway, Chin. Herb. Med. 15 (2023) 556-563.
|
| [15] |
J. Flores, A. Noel, B. Foveau, et al., Caspase-1 inhibition alleviates cognitive impairment and neuropathology in an Alzheimer’s disease mouse model, Nat. Commun. 9 (2018), 3916.
|
| [16] |
W. Xin, S. Gong, Y. Chen, et al., Self-assembling P38 peptide inhibitor nanoparticles ameliorate the transition from acute to chronic kidney disease by suppressing ferroptosis, Adv. Healthc. Mater. 13 (2024), e2400441.
|
| [17] |
X. Yang, D. Thorngren, Q. Chen, et al., Protective role of relaxin in a mouse model of aristolochic acid nephropathy, Biomed Pharmacother. 115 (2019), 108917.
|
| [18] |
Y. Bai, W. Wang, P. Yin, et al., Ruxolitinib alleviates renal interstitial fibrosis in uuo mice, Int. J. Biol. Sci. 16 (2020) 194-203.
|
| [19] |
C. Huang, L. Cheng, X. Feng, et al., Dencichine ameliorates renal injury by improving oxidative stress, apoptosis and fibrosis in diabetic rats, Life Sci. 258 (2020), 118146.
|
| [20] |
M. Zhu, H. Wang, J. Chen, et al., Sinomenine improve diabetic nephropathy by inhibiting fibrosis and regulating the JAK2/STAT3/SOCS1 pathway in streptozotocin-induced diabetic rats, Life Sci. 265 (2021), 118855.
|
| [21] |
D. Li, K. Yu, F. Feng, et al., Hydroxychloroquine alleviates renal interstitial fibrosis by inhibiting the PI3K/Akt signaling pathway, Biochem Biophys Res Commun. 610 (2022) 154-161.
|
| [22] |
S. Zhou, Y. He, W. Zhang, et al., Ophiocordyceps lanpingensis polysaccharides alleviate chronic kidney disease through MAPK/NF-κB pathway, J. Ethnopharmacol. 276 (2021), 114189.
|
| [23] |
J. Shi, S. Li, L. Yi, et al., Levistolide a attenuates acute kidney injury in mice by inhibiting the TLR-4/NF-κB pathway, Drug Des. Devel. Ther. 18 (2024) 5583-5597.
|
| [24] |
W.A. Keshk, S.M. Zahran, Mechanistic role of cAMP and hepatocyte growth factor signaling in thioacetamide-induced nephrotoxicity: Unraveling the role of platelet rich plasma, Biomed. Pharmacother. 109 (2019) 1078-1084.
|
| [25] |
N.M. Mahmoud, S.M. Elshazly, S. Rezq, Geraniol protects against cyclosporine A-induced renal injury in rats: Role of Wnt/β-catenin and PPARγ signaling pathways, Life Sci. 291 (2022), 120259.
|
| [26] |
M.R. Afrin, S. Arumugam, M.A. Rahman, et al., Curcumin reduces the risk of chronic kidney damage in mice with nonalcoholic steatohepatitis by modulating endoplasmic reticulum stress and MAPK signaling, Int. Immunopharmacol. 49 (2017) 161-167.
|
| [27] |
L. Guo, K. Tan, Q. Luo, et al., Dihydromyricetin promotes autophagy and attenuates renal interstitial fibrosis by regulating miR-155-5p/PTEN signaling in diabetic nephropathy, Bosn J Basic Med Sci. 20 (2020) 372-380.
|
| [28] |
X. Liu, J. Chen, N. Sun, et al., Ginsenoside Rb1 ameliorates autophagy via the AMPK/mTOR pathway in renal tubular epithelial cells in vitro and in vivo, Int. J. Biol. Macromol. 163 (2020) 996-1009.
|
| [29] |
Y. Tu, L. Gu, D. Chen, et al., Rhein inhibits autophagy in rat renal tubular cells by regulation of AMPK/mTOR signaling, Sci. Rep. 7 (2017), 43790.
|
| [30] |
T. Dusabimana, E.J. Park, J. Je, et al., Geniposide improves diabetic nephropathy by enhancing ULK1-mediated autophagy and reducing oxidative stress through AMPK activation, Int. J. Mol. Sci. 22 (2021), 1651.
|
| [31] |
M. Tao, D. Zheng, X. Liang, et al., Tripterygium glycoside suppresses epithelial-to-mesenchymal transition of diabetic kidney disease podocytes by targeting autophagy through the mTOR/Twist1 pathway, Mol. Med. Rep. 24 (2021), 592.
|
| [32] |
X.Y. Li, S.S. Wang, Z. Han, et al., Triptolide restores autophagy to alleviate diabetic renal fibrosis through the miR-141-3p/PTEN/Akt/mTOR pathway, Mol Ther Nucleic Acids. 35 (2024), 102343.
|
| [33] |
F. Yang, Y. Zhang, L. Dong, et al., Cordyceps cicadae ameliorates inflammatory responses, oxidative stress, and fibrosis by targeting the PI3K/mTOR-mediated autophagy pathway in the renal of MRL/lpr mice, Immun Inflamm Dis. 12 (2024), e1168.
|
| [34] |
Y.C. Han, S.Q. Tang, Y.T. Liu, et al., AMPK agonist alleviate renal tubulointerstitial fibrosis via activating mitophagy in high fat and streptozotocin induced diabetic mice, Cell Death Dis. 12 (2021), 925.
|
| [35] |
Y.H. Ling, S.M. Krishnan, C.T. Chan, et al., Anakinra reduces blood pressure and renal fibrosis in one kidney/DOCA/salt-induced hypertension, Pharmacol. Res. 116 (2017) 77-86.
|
| [36] |
V. Masola, A. Carraro, S. Granata, et al., In vitro effects of interleukin (IL)-1 beta inhibition on the epithelial-to-mesenchymal transition (EMT) of renal tubular and hepatic stellate cells, J. Transl. Med. 17 (2019), 12.
|
| [37] |
K.H. Kim, I.S. Lee, J.Y. Park, et al., Cucurbitacin B induces hypoglycemic effect in diabetic mice by regulation of AMP-activated protein kinase alpha and glucagon-like peptide-1 via bitter taste receptor signaling, Front. Pharmacol. 9 (2018), 1071.
|
| [38] |
M. Wu, Z. Yang, C. Zhang, et al., Inhibition of NLRP3 inflammasome ameliorates podocyte damage by suppressing lipid accumulation in diabetic nephropathy, Metabolism 118 (2021), 154748.
|
| [39] |
Z. Yang, Y. He, Q. Ma, et al., Alleviative effect of melatonin against the nephrotoxicity induced by cadmium exposure through regulating renal oxidative stress, inflammatory reaction, and fibrosis in a mouse model, Ecotoxicol. Environ. Saf. 265 (2023), 115536.
|
| [40] |
Z. Ma, L. Zhu, S. Wang, et al., Berberine protects diabetic nephropathy by suppressing epithelial-to-mesenchymal transition involving the inactivation of the NLRP3 inflammasome, Ren. Fail. 44 (2022) 923-932.
|
| [41] |
K. El Karoui, A. Viau, O. Dellis, et al., Endoplasmic reticulum stress drives proteinuria-induced kidney lesions via Lipocalin 2, Nat. Commun. 7 (2016), 10330.
|
| [42] |
J. Chen, Z. Ou, T. Gao, et al., Ginkgolide B alleviates oxidative stress and ferroptosis by inhibiting GPX4 ubiquitination to improve diabetic nephropathy, Biomed Pharmacother. 156 (2022), 113953.
|
| [43] |
B. Zhang, X. Chen, F. Ru, et al., Liproxstatin-1 attenuates unilateral ureteral obstruction-induced renal fibrosis by inhibiting renal tubular epithelial cells ferroptosis, Cell Death Dis. 12 (2021), 843.
|
| [44] |
B. Wang, L.N. Yang, L.T. Yang, et al., Fisetin ameliorates fibrotic kidney disease in mice via inhibiting ACSL4-mediated tubular ferroptosis, Acta Pharmacol Sin. 45 (2024) 150-165.
|
| [45] |
C.W. Qiu, B. Chen, H.F. Zhu, et al., Gastrodin alleviates cisplatin nephrotoxicity by inhibiting ferroptosis via the SIRT1/FOXO3A/GPX4 signaling pathway, J. Ethnopharmacol. 319 (2024), 117282.
|
| [46] |
S. Yang, T. Pei, L. Wang, et al., Salidroside alleviates renal fibrosis in SAMP8 mice by inhibiting ferroptosis, Molecules 27 (2022), 8039.
|
| [47] |
Y.H. Lo, S. Yang, C.C. Cheng, et al., Nobiletin alleviates ferroptosis-associated renal injury, inflammation, and fibrosis in a unilateral ureteral obstruction mouse model, Biomedicines 10 (2022), 595.
|
| [48] |
B. Hou, P. Ma, X. Yang, et al., In silico prediction and experimental validation to reveal the protective mechanism of Puerarin against excessive extracellular matrix accumulation through inhibiting ferroptosis in diabetic nephropathy, J. Ethnopharmacol. 391 (2024), 117281.
|
| [49] |
L. Yang, J. Guo, N. Yu, et al., Tocilizumab mimotope alleviates kidney injury and fibrosis by inhibiting IL-6 signaling and ferroptosis in UUO model, Life Sci. 261 (2020), 118487.
|
| [50] |
Y. Ye, A. Chen, L. Li, et al., Repression of the antiporter SLC7A11/glutathione/glutathione peroxidase 4 axis drives ferroptosis of vascular smooth muscle cells to facilitate vascular calcification, Kidney Int. 102 (2022) 1259-1275.
|
| [51] |
C. Li, N. Xie, Y. Li, et al., N-acetylcysteine ameliorates cisplatin-induced renal senescence and renal interstitial fibrosis through sirtuin1 activation and p53 deacetylation, Free Radic. Biol. Med. 130 (2019) 512-527.
|
| [52] |
J. Song, H. Wang, J. Sheng, et al., Vitexin attenuates chronic kidney disease by inhibiting renal tubular epithelial cell ferroptosis via NRF2 activation, Mol. Med. 29 (2023), 147.
|
| [53] |
A. Linkermann, R. Skouta, N. Himmerkus, et al., Synchronized renal tubular cell death involves ferroptosis, Proc. Natl. Acad. Sci. U. S. A. 111 (2014) 16836-16841.
|
| [54] |
X. Chen, C. Zhuang, Y. Ren, et al., Identification of the Raf kinase inhibitor TAK-632 and its analogues as potent inhibitors of necroptosis by targeting RIPK1 and RIPK3, Br. J. Pharmacol. 176 (2019) 2095-2108.
|
| [55] |
S. Prajapati, B. Tomar, A. Srivastava, et al., 6, 7-Dihydroxycoumarin ameliorates crystal-induced necroptosis during crystal nephropathies by inhibiting MLKL phosphorylation, Life Sci. 271 (2021), 119193.
|
| [56] |
C. Rui, S. Shi, W. Ren, et al., The multitargeted kinase inhibitor KW-2449 ameliorates cisplatin-induced nephrotoxicity by targeting RIPK1-mediated necroptosis, Biochem. Pharmacol. 188 (2021), 114542.
|
| [57] |
W. Liu, B. Chen, Y. Wang, et al., RGMb protects against acute kidney injury by inhibiting tubular cell necroptosis via an MLKL-dependent mechanism, Proc. Natl. Acad. Sci. U. S. A. 115 (2018) 1475-1484.
|
| [58] |
F. Maremonti, C. Meyer, A. Linkermann, Mechanisms and models of kidney tubular necrosis and nephron loss, J. Am. Soc. Nephrol. 33 (2022) 472-486.
|
| [59] |
Y.A. Lazebnik, S.H. Kaufmann, S. Desnoyers, et al., Cleavage of poly(ADP-ribose) polymerase by a proteinase with properties like ICE, Nature 371 (1994) 346-347.
|
| [60] |
D. Moujalled, A.G. Southon, E. Saleh, et al., BH3 mimetic drugs cooperate with Temozolomide, JQ1 and inducers of ferroptosis in killing glioblastoma multiforme cells, Cell Death Differ. 29 (2022) 1335-1348.
|
| [61] |
Y. Bao, Q. Yang, X. Shen, et al., Targeting tumor suppressor p53 for organ fibrosis therapy, Cell Death Dis. 15 (2024), 336.
|
| [62] |
E.H.Y. Cheng, T.V. Sheiko, J.K. Fisher, et al., VDAC2 inhibits BAK activation and mitochondrial apoptosis, Science 301 (2003) 513-517.
|
| [63] |
X. Yang, D.M. Okamura, X. Lu, et al., CD36 in chronic kidney disease: Novel insights and therapeutic opportunities, Nat. Rev. Nephrol. 13 (2017) 769-781.
|
| [64] |
C. Kuppe, M.M. Ibrahim, J. Kranz, et al., Decoding myofibroblast origins in human kidney fibrosis, Nature 589 (2021) 281-286.
|
| [65] |
X. Chen, L. Gu, X. Cheng, et al., miR-17-5p downregulation alleviates apoptosis and fibrosis in high glucose-induced human mesangial cells through inactivation of Wnt/β-catenin signaling by targeting KIF23, Environ. Toxicol. 36 (2021) 1702-1712.
|
| [66] |
T. Ma, H. Li, H. Liu, et al., Neat1 promotes acute kidney injury to chronic kidney disease by facilitating tubular epithelial cells apoptosis via sequestering miR-129-5p, Mol. Ther. 30 (2022) 3313-3332.
|
| [67] |
S. Hu, R. Han, J. Shi, et al., The long noncoding RNA LOC105374325 causes podocyte injury in individuals with focal segmental glomerulosclerosis, J. Biol. Chem. 293 (2018) 20227-20239.
|
| [68] |
B. Tang, W. Li, T. Ji, et al., Circ-AKT3 inhibits the accumulation of extracellular matrix of mesangial cells in diabetic nephropathy via modulating miR-296-3p/E-cadherin signals, J. Cell. Mol. Med. 24 (2020) 8779-8788.
|
| [69] |
P. Codogno, M. Mehrpour, T. Proikas-Cezanne, Canonical and non-canonical autophagy: Variations on a common theme of self-eating Nat. Rev. Mol. Cell Biol. 13 (2011) 7-12.
|
| [70] |
G. Kroemer, B. Levine, Autophagic cell death: The story of a misnomer, Nat. Rev. Mol. Cell Biol. 9 (2008) 1004-1010.
|
| [71] |
S. Bialik, S.K. Dasari, A. Kimchi, Autophagy-dependent cell death - where, how and why a cell eats itself to death, J. Cell Sci. 131 (2018), jcs215152.
|
| [72] |
M.J. Livingston, H. Ding, S. Huang, et al., Persistent activation of autophagy in kidney tubular cells promotes renal interstitial fibrosis during unilateral ureteral obstruction, Autophagy 12 (2016) 976-998.
|
| [73] |
O. Lenoir, M. Jasiek, C. Henique, et al., Endothelial cell and podocyte autophagy synergistically protect from diabetes-induced glomerulosclerosis, Autophagy 11 (2015) 1130-1145.
|
| [74] |
S. Shang, X. Li, H. Wang, et al., Targeted therapy of kidney disease with nanoparticle drug delivery materials, Bioact. Mater. 37 (2024) 206-221.
|
| [75] |
Y. Ding, S.L. Kim, S.Y. Lee, et al., Autophagy regulates TGF-β expression and suppresses kidney fibrosis induced by unilateral ureteral obstruction, J. Am. Soc. Nephrol. 25 (2014) 2835-2846.
|
| [76] |
J. Li, M. Xiong, X. Fu, et al., Determining a multimodal aging clock in a cohort of Chinese women, Med 4 (2023) 825-848.e13.
|
| [77] |
M. Jiang, S. Wu, K. Xie, et al., The significance of ferroptosis in renal diseases and its therapeutic potential, Heliyon 10 (2024), e35882.
|
| [78] |
X. Zhou, R. Zhao, M. Lv, et al., ACSL4 promotes microglia-mediated neuroinflammation by regulating lipid metabolism and VGLL4 expression, Brain Behav. Immun. 109 (2023) 331-343.
|
| [79] |
A. Gupta, S. Chakole, S. Agrawal, et al., Emerging insights into necroptosis: Implications for renal health and diseases, Cureus 15 (2023), e43609.
|
| [80] |
E.E. Elias, B. Lyons, D.A. Muruve, Gasdermins and pyroptosis in the kidney, Nat. Rev. Nephrol. 19 (2023) 337-350.
|
| [81] |
I. Amador-Martinez, O.E. Aparicio-Trejo, B. Bernabe-Yepes, et al., Mitochondrial impairment: A link for inflammatory responses activation in the cardiorenal syndrome type 4, Int. J. Mol. Sci. 24 (2023), 15875.
|
| [82] |
A. Mueller, Y. Zhao, H. Cicek, et al., Transcriptional and clonal characterization of cytotoxic T cells in crescentic glomerulonephritis, J. Am. Soc. Nephrol. 34 (2023) 1003-1018.
|
| [83] |
Q. Cheng, J. Pan, Z. Zhou, et al., Caspase-11/4 and gasdermin D-mediated pyroptosis contributes to podocyte injury in mouse diabetic nephropathy, Acta Pharmacol. Sin. 42 (2021) 954-963.
|
| [84] |
Y. Wang, B. Jiao, Z. Hu, et al., Critical Role of histone deacetylase 3 in the regulation of kidney inflammation and fibrosis, Kidney Int. 105 (2024) 775-790.
|
| [85] |
S.J. Dixon, K.M. Lemberg, M.R. Lamprecht, et al., Ferroptosis: An iron-dependent form of nonapoptotic cell death, Cell 149 (2012) 1060-1072.
|
| [86] |
B.R. Stockwell, Ferroptosis turns 10: Emerging mechanisms, physiological functions, and therapeutic applications, Cell 185 (2022) 2401-2421.
|
| [87] |
J.P.F. Angeli, M. Schneider, B. Proneth, et al., Inactivation of the ferroptosis regulator Gpx4 triggers acute renal failure in mice, Nat. Cell Biol. 16 (2014) 1180-1191.
|
| [88] |
L. Gao, J. Zhang, T. Yang, et al., STING/ACSL4 axis-dependent ferroptosis and inflammation promote hypertension-associated chronic kidney disease, Mol. Ther. 31 (2023) 3084-3103.
|
| [89] |
Y. Dai, Y. Chen, D. Mo, et al., Inhibition of ACSL4 ameliorates tubular ferroptotic cell death and protects against fibrotic kidney disease, Commun. Biol. 6 (2023), 907.
|
| [90] |
K. Bersuker, J.M. Hendricks, Z. Li, et al., The CoQ oxidoreductase FSP1 acts parallel to GPX4 to inhibit ferroptosis, Nature 575 (2019) 688-692.
|
| [91] |
Q. Ru, Y. Li, L. Chen, et al., Iron homeostasis and ferroptosis in human diseases: Mechanisms and therapeutic prospects, Signal Transduct. Target. Ther. 9 (2024), 271.
|
| [92] |
L. Galluzzi, O. Kepp, F.K. Chan, et al., Necroptosis: Mechanisms and relevance to disease, Annu. Rev. Pathol. 12 (2017) 103-130.
|
| [93] |
S. Grootjans, T. Vanden Berghe, P. Vandenabeele, Initiation and execution mechanisms of necroptosis: An overview, Cell Death Differ. 24 (2017) 1184-1195.
|
| [94] |
K. Newton, K.E. Wickliffe, D.L. Dugger, et al., Cleavage of RIPK1 by caspase-8 is crucial for limiting apoptosis and necroptosis, Nature 574 (2019) 428-431.
|
| [95] |
A. Sureshbabu, E. Patino, K.C. Ma, et al., RIPK3 promotes sepsis-induced acute kidney injury via mitochondrial dysfunction, JCI Insight 3 (2018), e98411.
|
| [96] |
A. Srivastava, B. Tomar, P. Sharma, et al., RIPK3-MLKL signaling activates mitochondrial CaMKII and drives intrarenal extracellular matrix production during CKD, Matrix Biol. 112 (2022) 72-89.
|
| [97] |
Y. Wang, L. Yu, Y. Li, et al., Supplemented Gegen Qinlian Decoction Formula attenuates podocyte mitochondrial fission and renal fibrosis in diabetic kidney disease by inhibiting TNF-α-mediated necroptosis, compared with empagliflozin, J. Ethnopharmacol. 334 (2024), 118572.
|
| [98] |
Z. Lin, A. Chen, H. Cui, et al., Renal tubular epithelial cell necroptosis promotes tubulointerstitial fibrosis in patients with chronic kidney disease, FASEB J. 36 (2022), e22625.
|
| [99] |
N. Pandian, T.D. Kanneganti, PANoptosis: A unique innate immune inflammatory cell death modality, J. Immunol. 209 (2022) 1625-1633.
|
| [100] |
A.B. Singh, V. Kaushal, J.K. Megyesi, et al., Cloning and expression of rat caspase-6 and its localization in renal ischemia/reperfusion injury, Kidney Int. 62 (2002) 106-115.
|
| [101] |
A. Ortiz, P. Justo, A. Sanz, et al., Targeting apoptosis in acute tubular injury, Biochem. Pharmacol. 66 (2003) 1589-1594.
|
| [102] |
T. Muller, C. Dewitz, J. Schmitz, et al., Necroptosis and ferroptosis are alternative cell death pathways that operate in acute kidney failure, Cell. Mol. Life Sci. 74 (2017) 3631-3645.
|
| [103] |
D. Martin-Sanchez, M. Fontecha-Barriuso, S. Carrasco, et al., TWEAK and RIPK1 mediate a second wave of cell death during AKI, Proc. Natl. Acad. Sci. U. S. A. 115 (2018) 4182-4187.
|
| [104] |
B.J. Aubrey, G.L. Kelly, A. Janic, et al., How does p53 induce apoptosis and how does this relate to p53-mediated tumour suppression Cell Death Differ. 25 (2018) 104-113.
|
| [105] |
Y. Liu, B.R. Stockwell, X. Jiang, et al., p53-regulated non-apoptotic cell death pathways and their relevance in cancer and other diseases, Nat. Rev. Mol. Cell Biol. (2025).
|
| [106] |
R. Kang, H.J. Zeh, M.T. Lotze, et al., The Beclin 1 network regulates autophagy and apoptosis, Cell Death Differ. 18 (2011) 571-580.
|
| [107] |
D.H. Kim, J.S. Park, H.I. Choi, et al., The critical role of FXR is associated with the regulation of autophagy and apoptosis in the progression of AKI to CKD, Cell Death Dis. 12 (2021), 320.
|
| [108] |
F. Radogna, M. Dicato, M. Diederich, Cancer-type-specific crosstalk between autophagy, necroptosis and apoptosis as a pharmacological target, Biochem. Pharmacol. 94 (2015) 1-11.
|
| [109] |
Y. Xie, R. Kang, D.J. Klionsky, et al., GPX4 in cell death, autophagy, and disease, Autophagy 19 (2023) 2621-2638.
|
| [110] |
D. Bertheloot, E. Latz, B.S. Franklin, Necroptosis, pyroptosis and apoptosis: An intricate game of cell death, Cell. Mol. Immunol. 18 (2021) 1106-1121.
|
| [111] |
M. Wu, Q. Jin, X. Xu, et al., TP53RK drives the progression of chronic kidney disease by phosphorylating Birc5, Adv. Sci. 10 (2023), e2301753.
|
| [112] |
Y. Tao, J. Lu, X. Du, et al., Survivin selective inhibitor YM155 induce apoptosis in SK-NEP-1 Wilms tumor cells, BMC Cancer 12 (2012), 619.
|
| [113] |
R. Wang, W. Yuan, L. Li, et al., Resveratrol ameliorates muscle atrophy in chronic kidney disease via the axis of SIRT1/FoxO1, Phytother. Res. 36 (2022) 3265-3275.
|
| [114] |
J. Li, Q. Duan, X. Wei, et al., Kidney-targeted nanoparticles loaded with the natural antioxidant rosmarinic acid for acute kidney injury treatment, Small 18 (2022), e2204388.
|
| [115] |
X. Hu, L. Gan, Z. Tang, et al., A natural small molecule mitigates kidney fibrosis by targeting Cdc42-mediated GSK-3β/β-catenin signaling, Adv. Sci. 11 (2024), e2307850.
|
| [116] |
L.J. Hickson, L.G.P. Langhi Prata, S.A. Bobart, et al., Senolytics decrease senescent cells in humans: Preliminary report from a clinical trial of Dasatinib plus Quercetin in individuals with diabetic kidney disease, EBioMedicine 47 (2019) 446-456.
|
| [117] |
H. Birn, The kidney in vitamin B12 and folate homeostasis: Characterization of receptors for tubular uptake of vitamins and carrier proteins, Am. J. Physiol. Renal Physiol. 291 (2006) F22-F36.
|
| [118] |
K. Kumar, K. Bosch, V. Vemuri, et al., Withaferin A ameliorates ovarian cancer-induced renal damage through the regulation of expression of inflammatory cytokines, J. Ovarian Res. 17 (2024), 199.
|
| [119] |
C. Liu, X. Wang, X. Wang, et al., A new LKB1 activator, piericidin analogue S14, retards renal fibrosis through promoting autophagy and mitochondrial homeostasis in renal tubular epithelial cells, Theranostics 12 (2022) 7158-7179.
|
| [120] |
J. Bao, Y. Shi, M. Tao, et al., Pharmacological inhibition of autophagy by 3-MA attenuates hyperuricemic nephropathy, Clin. Sci. 132 (2018) 2299-2322.
|
| [121] |
K. Schmucki, P. Hofmann, T. Fehr, et al., Mammalian target of rapamycin inhibitors and kidney function after thoracic transplantation: A systematic review and recommendations for management of lung transplant recipients, Transplantation 107 (2023) 53-73.
|
| [122] |
H. Ren, Y. Shao, C. Wu, et al., Metformin alleviates oxidative stress and enhances autophagy in diabetic kidney disease via AMPK/SIRT1-FoxO1 pathway, Mol. Cell. Endocrinol. 500 (2020), 110628.
|
| [123] |
C. Zheng, Y. Hou, K.W. Tsai, et al., Resveratrol mitigates uremic toxin-induced intestinal barrier dysfunction in chronic kidney disease by promoting mitophagy and inhibiting apoptosis pathways, Int. J. Med. Sci. 21 (2024) 2437-2449.
|
| [124] |
A.K. Aranda-Rivera, A. Cruz-Gregorio, O.E. Aparicio-Trejo, et al., Sulforaphane protects against unilateral ureteral obstruction-induced renal damage in rats by alleviating mitochondrial and lipid metabolism impairment, Antioxidants 11 (2022), 1854.
|
| [125] |
C. Ren, X. Bao, X. Lu, et al., Complanatoside A targeting NOX4 blocks renal fibrosis in diabetic mice by suppressing NLRP3 inflammasome activation and autophagy, Phytomedicine 104 (2022), 154310.
|
| [126] |
S. Wen, F. Deng, L. Li, et al., VX-765 ameliorates renal injury and fibrosis in diabetes by regulating caspase-1-mediated pyroptosis and inflammation, J. Diabetes Investig. 13 (2022) 22-33.
|
| [127] |
A. Dhorepatil, S. Ball, R.K. Ghosh, et al., Canakinumab: Promises and future in cardiometabolic diseases and malignancy, Am. J. Med. 132 (2019) 312-324.
|
| [128] |
P.M. Ridker, J.G. MacFadyen, R.J. Glynn, et al., Inhibition of interleukin-1β by canakinumab and cardiovascular outcomes in patients with chronic kidney disease, J. Am. Coll. Cardiol. 71 (2018) 2405-2414.
|
| [129] |
Q. Wu, Y. Guan, K. Zhang, et al., Tanshinone IIA mediates protection from diabetes kidney disease by inhibiting oxidative stress induced pyroptosis, J. Ethnopharmacol. 316 (2023), 116667.
|
| [130] |
J. Li, L. Lv, M. Hu, et al., Inhibition of N6-methyladenosine methylation of ASC by berberine ameliorates pyroptosis of renal tubular epithelial cells in acute kidney injury, Cell. Signal. 131 (2025), 111732.
|
| [131] |
H. Yosri, D.H. El-Kashef, M. El-Sherbiny, et al., Calycosin modulates NLRP3 and TXNIP-mediated pyroptotic signaling and attenuates diabetic nephropathy progression in diabetic rats; An insight, Biomed. Pharmacother. 155 (2022), 113758.
|
| [132] |
Z. Zhao, J. Wu, H. Xu, et al., XJB-5-131 inhibited ferroptosis in tubular epithelial cells after ischemia-reperfusion injury, Cell Death Dis. 11 (2020), 629.
|
| [133] |
G. Jones, L. Zeng, J. Kim, Mechanism-based pharmacokinetic modeling of absorption and disposition of a deferoxamine-based nanochelator in rats, Mol. Pharm. 20 (2023) 481-490.
|
| [134] |
M. Guerrero-Hue, C. Garcia-Caballero, A. Palomino-Antolin, et al., Curcumin reduces renal damage associated with rhabdomyolysis by decreasing ferroptosis-mediated cell death, FASEB J. 33 (2019) 8961-8975.
|
| [135] |
Y. Wang, F. Quan, Q. Cao, et al., Quercetin alleviates acute kidney injury by inhibiting ferroptosis, J. Adv. Res. 28 (2020) 231-243.
|
| [136] |
A. Linkermann, J.H. Brasen, N. Himmerkus, et al., Rip1 (receptor-interacting protein kinase 1) mediates necroptosis and contributes to renal ischemia/reperfusion injury, Kidney Int. 81 (2012) 751-761.
|
| [137] |
S. Hofmans, L. Devisscher, S. Martens, et al., Tozasertib analogues as inhibitors of necroptotic cell death, J. Med. Chem. 61 (2018) 1895-1920.
|
| [138] |
P. Mandal, S.B. Berger, S. Pillay, et al., RIP3 induces apoptosis independent of pronecrotic kinase activity, Mol. Cell 56 (2014) 481-495.
|
| [139] |
C. Xu, J. Wang, X. Suo, et al., RIPK3 inhibitor-AZD5423 alleviates acute kidney injury by inhibiting necroptosis and inflammation, Int. Immunopharmacol. 112 (2022), 109262.
|
| [140] |
J. Guo, J. Hu, M. Liu, et al., Apigenin-mediated ESCRT-III activation and mitophagy alleviate LPS-induced necroptosis in renal cells, J. Agric. Food Chem. 73 (2025) 9906-9919.
|
| [141] |
O. Egbuna, B. Zimmerman, G. Manos, et al., Inaxaplin for proteinuric kidney disease in persons with two APOL1 variants, N. Engl. J. Med. 388 (2023) 969-979.
|
| [142] |
T.B. Huber, G. Walz, E. Wolfgang Kuehn, mTOR and rapamycin in the kidney: Signaling and therapeutic implications beyond immunosuppression, Kidney Int. 79 (2011) 502-511.
|
| [143] |
H. Ushijima, R. Monzaki, An in vitro evaluation of the antioxidant activities of necroptosis and apoptosis inhibitors: The potential of necrostatin-1 and necrostatin-1i to have radical scavenging activities, Pharmacol. Rep. 75 (2023) 490-497.
|
| [144] |
J. Xie, Z. Ye, L. Li, et al., Ferrostatin-1 alleviates oxalate-induced renal tubular epithelial cell injury, fibrosis and calcium oxalate stone formation by inhibiting ferroptosis, Mol. Med. Rep. 26 (2022), 256.
|
| [145] |
J.D. Yang, S.C. Lin, H.L. Kuo, et al., Imperatorin ameliorates ferroptotic cell death, inflammation, and renal fibrosis in a unilateral ureteral obstruction mouse model, Phytomedicine 135 (2024), 156066.
|
| [146] |
Q. Pang, P. Wang, Y. Pan, et al., Irisin protects against vascular calcification by activating autophagy and inhibiting NLRP3-mediated vascular smooth muscle cell pyroptosis in chronic kidney disease, Cell Death Dis. 13 (2022), 283.
|
| [147] |
Y. Cheng, Z. Lu, T. Mao, et al., Magnoflorine ameliorates chronic kidney disease in high-fat and high-fructose-fed mice by promoting parkin/PINK1-dependent mitophagy to inhibit NLRP3/caspase-1-mediated pyroptosis, J. Agric. Food Chem. 72 (2024) 12775-12787.
|
| [148] |
L. Xiao, X. Xu, F. Zhang, et al., The mitochondria-targeted antioxidant MitoQ ameliorated tubular injury mediated by mitophagy in diabetic kidney disease via Nrf2/PINK1, Redox Biol. 11 (2017) 297-311.
|
| [149] |
J. Li, J. Yang, Q. Xian, et al., Kaempferitrin attenuates unilateral ureteral obstruction-induced renal inflammation and fibrosis in mice by inhibiting NOX4-mediated tubular ferroptosis, Phytother. Res. 38 (2024) 2656-2668.
|
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