Exploring TGFBR3 in disease pathogenesis: Mechanisms, clinical implications, and pharmacological modulation

Hui Song; Jinjiang Chou; Peng Zhao; Meijun Chen; Jue Yang; Xiaojiang Hao

doi:10.1016/j.jpha.2025.101372

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Hui Song, Jinjiang Chou, Peng Zhao, Meijun Chen, Jue Yang, Xiaojiang Hao. Exploring TGFBR3 in disease pathogenesis: Mechanisms, clinical implications, and pharmacological modulation[J]. Journal of Pharmaceutical Analysis. doi: 10.1016/j.jpha.2025.101372

Citation:

Hui Song, Jinjiang Chou, Peng Zhao, Meijun Chen, Jue Yang, Xiaojiang Hao. Exploring TGFBR3 in disease pathogenesis: Mechanisms, clinical implications, and pharmacological modulation[J]. Journal of Pharmaceutical Analysis. doi: 10.1016/j.jpha.2025.101372

Citation:

Hui Song, Jinjiang Chou, Peng Zhao, Meijun Chen, Jue Yang, Xiaojiang Hao. Exploring TGFBR3 in disease pathogenesis: Mechanisms, clinical implications, and pharmacological modulation[J]. Journal of Pharmaceutical Analysis. doi: 10.1016/j.jpha.2025.101372

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Exploring TGFBR3 in disease pathogenesis: Mechanisms, clinical implications, and pharmacological modulation

doi: 10.1016/j.jpha.2025.101372

Hui Song^a,b,
Jinjiang Chou^c,
Peng Zhao^a,d,
Meijun Chen^a,d,
Jue Yang^{a,d
,
,},
Xiaojiang Hao^{a,d
,
,}

a. Key Laboratory of Endemic and Ethnic Diseases, Ministry of Education & State Key Laboratory of Discovery and Utilization of Functional Components in Traditional Chinese Medicine, Guizhou Medical University, Guiyang, 550004, China;
b. Key Laboratory of Medical Molecular Biology of Guizhou Province, Guiyang, 550004, China;
c. Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, 17165, Sweden;
d. Natural Products Research Center of Guizhou Province, Guiyang, 550014, China

Funds:

This study was funded by grants from the National Natural Science Foundation of China (Grant Nos.: 82304348, 82160823, and 32060210), 2022 Guiyang Science and Technology Talent Training Project (Project No.: [2023]48-5), Guizhou Science and Technology Innovation Talent Team (Grant No.: QKHPTRC-CXTD [2022]007), and Guizhou Medical University (Grant No.: [2024]011).

Received Date: Nov. 18, 2024
Accepted Date: Jun. 16, 2025
Rev Recd Date: May 25, 2025
Available Online: Jun. 21, 2025

Abstract

Abstract

Transforming growth factor beta (TGF-β) receptor 3 (TGFBR3), or betaglycan, is a transmembrane proteoglycan that serves as a coreceptor for TGF-β ligands, modulating TGF-β signaling in a context-dependent manner. Its extracellular domain can undergo proteolytic cleavage, yielding a 120 kDa soluble isoform (sTGFBR3) that antagonizes TGF-β signaling by sequestering ligands. Through this dual role, TGFBR3 exerts profound influence over various physiological and pathological processes, including cell survival, stemness, differentiation, cancer metastasis, chemoresistance, and fibrosis, underscoring its significance as both a biomarker and therapeutic target. Despite its significance, regulatory mechanisms, particularly tissue-specific expression, cross-talk with other pathways and post-translational modifications, remain poorly defined. A current thorough review of the prognostic and therapeutic implications of TGFBR3 is still lacking. In this review, we systematically examine the structural features of TGFBR3, and their functional relevance, providing an in-depth analysis of its dysregulation and molecular roles in diseases such as cancer, nervous system disorders, cardiovascular diseases (CVDs), diabetes and infectious diseases. Current experimental approaches are critically evaluated, and gaps in existing literature are highlighted to identify priorities for future research. By synthesizing emerging insights, this review aims to inform the development of TGFBR3-targeted therapies and support the design of innovative clinical and preclinical strategies.
- TGFBR3,
- Cancer,
- Diabetes,
- Epigenetic modifications,
- Pharmaceutical interventions

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References(150)

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