Prrx1 promotes mesangial cell proliferation and kidney fibrosis through YAP in diabetic nephropathy

Liu Xu; Jiasen Shi; Huan Li; Yunfei Liu; Jingyi Wang; Xizhi Li; Dongxue Ren; Sijie Liu; Heng Wang; Yinfei Lu; Jinfang Song; Lei Du; Qian Lu; Xiaoxing Yin

doi:10.1016/j.jpha.2025.101247

Volume 15 Issue 10

Oct. 2025

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Article Navigation > Journal of Pharmaceutical Analysis > 2025 > 15(10): 101247

Liu Xu, Jiasen Shi, Huan Li, Yunfei Liu, Jingyi Wang, Xizhi Li, Dongxue Ren, Sijie Liu, Heng Wang, Yinfei Lu, Jinfang Song, Lei Du, Qian Lu, Xiaoxing Yin. Prrx1 promotes mesangial cell proliferation and kidney fibrosis through YAP in diabetic nephropathy[J]. Journal of Pharmaceutical Analysis, 2025, 15(10): 101247. doi: 10.1016/j.jpha.2025.101247

Citation:

Liu Xu, Jiasen Shi, Huan Li, Yunfei Liu, Jingyi Wang, Xizhi Li, Dongxue Ren, Sijie Liu, Heng Wang, Yinfei Lu, Jinfang Song, Lei Du, Qian Lu, Xiaoxing Yin. Prrx1 promotes mesangial cell proliferation and kidney fibrosis through YAP in diabetic nephropathy[J]. Journal of Pharmaceutical Analysis, 2025, 15(10): 101247. doi: 10.1016/j.jpha.2025.101247

Citation:

Liu Xu, Jiasen Shi, Huan Li, Yunfei Liu, Jingyi Wang, Xizhi Li, Dongxue Ren, Sijie Liu, Heng Wang, Yinfei Lu, Jinfang Song, Lei Du, Qian Lu, Xiaoxing Yin. Prrx1 promotes mesangial cell proliferation and kidney fibrosis through YAP in diabetic nephropathy[J]. Journal of Pharmaceutical Analysis, 2025, 15(10): 101247. doi: 10.1016/j.jpha.2025.101247

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Prrx1 promotes mesangial cell proliferation and kidney fibrosis through YAP in diabetic nephropathy

doi: 10.1016/j.jpha.2025.101247

a. Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou, Jiangsu, 221004, China;
b. Department of Clinical Pharmacy, Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, 221006, China;
c. Department of Neurology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, 221006, China

Funds:

The work was supported by the National Natural Science Foundation of China (Grant Nos.: 82273987, 81973377, and 82073906), and Postgraduate Research Practice Innovation Program of Jiangsu Province (Grant No.: KYCX23_2994).

Received Date: Nov. 07, 2024
Accepted Date: Feb. 21, 2025
Rev Recd Date: Jan. 22, 2025
Publish Date: Feb. 28, 2025

Abstract

Abstract

Mesangial cell proliferation is an early pathological indicator of diabetic nephropathy (DN). Growing evidence highlights the pivotal role of paired-related homeobox 1 (Prrx1), a key regulator of cellular proliferation and tissue differentiation, in various disease pathogenesis. Notably, Prrx1 is highly expressed in mesangial cells under DN conditions. Both in vitro and in vivo studies have demonstrated that Prrx1 overexpression promotes mesangial cell proliferation and contributes to renal fibrosis in db/m mice. Conversely, Prrx1 knockdown markedly suppresses hyperglycemia-induced mesangial cell proliferation and mitigates renal fibrosis in db/db mice. Mechanistically, Prrx1 directly interacts with the Yes-associated protein 1 (YAP) promoter, leading to the upregulation of YAP expression. This upregulation promotes mesangial cell proliferation and exacerbates renal fibrosis. These findings emphasize the crucial role of Prrx1 upregulation in high glucose-induced mesangial cell proliferation, ultimately leading to renal fibrosis in DN. Therefore, targeting Prrx1 to downregulate its expression presents a promising therapeutic strategy for treating renal fibrosis associated with DN.
- Diabetic nephropathy,
- Prrx1,
- Renal fibrosis,
- Mesangial cell,
- YAP

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References(50)

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