Unveiling the role of transgelin as a prognostic and therapeutic target in kidney fibrosis via a proteomic approach

Soie Kwon; Seongmin Cheon; Kyu-Hong Kim; Areum Seo; Eunjin Bae; Jae Wook Lee; Ran-Hui Cha; Jin Ho Hwang; Yong Chul Kim; Dong Ki Kim; Yon Su Kim; Dohyun Han; Seung-Hee Yang

doi:10.1038/s12276-024-01319-7

journal article Open Access Oct 07, 2024

Unveiling the role of transgelin as a prognostic and therapeutic target in kidney fibrosis via a proteomic approach

Soie Kwon

Seongmin Cheon

Kyu-Hong Kim Areum Seo Eunjin Bae Jae Wook Lee

Ran-Hui Cha Jin Ho Hwang Yong Chul Kim

Dong Ki Kim

Yon Su Kim

Dohyun Han

Seung-Hee Yang

Experimental & Molecular Medicine Vol. 56 No. 10 pp. 2296-2308 · Springer Science and Business Media LLC

View at Publisher Save 10.1038/s12276-024-01319-7

Abstract

AbstractChronic kidney disease (CKD) progression involves tubulointerstitial fibrosis, a process characterized by excessive extracellular matrix accumulation. To identify potential biomarkers for kidney fibrosis, we performed mass spectrometry-based proteomic profiling of human kidney tubular epithelial cells and kidney tissue from a 5/6 nephrectomy rat model. Multidisciplinary analysis across kidney fibrosis models revealed 351 differentially expressed proteins associated with kidney fibrosis, and they were enriched in processes related to the extracellular matrix, kidney aging, and mitochondrial functions. Network analysis of the selected proteins revealed five crucial proteins, of which transgelin emerged as a candidate protein that interacts with known fibrosis-related proteins. Concordantly, the gene expression of transgelin in the kidney tissue from the 5/6 nephrectomy model was elevated. Transgelin expression in kidney tissue gradually increased from intermediate to advanced fibrosis stages in 5/6 Nx rats and mice with unilateral ureteral obstruction. Subsequent validation in kidney tissue and urine samples from patients with CKD confirmed the upregulation of transgelin, particularly under advanced disease stages. Moreover, we investigated whether blocking TAGLN ameliorated kidney fibrosis and reduced reactive oxygen species levels in cellular models. In conclusion, our proteomic approach identified TAGLN as a potential noninvasive biomarker and therapeutic target for CKD-associated kidney fibrosis, suggesting its role in modulating mitochondrial dysfunction and oxidative stress responses.

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Details

Published: Oct 07, 2024
Vol/Issue: 56(10)
Pages: 2296-2308
License: View

Authors

Sanofi-aventis Korea, Seoul 06578, Republic of Korea

Funding

National Research Foundation of Korea Award: 2023R1A2C2006651

Cite This Article

Soie Kwon, Seongmin Cheon, Kyu-Hong Kim, et al. (2024). Unveiling the role of transgelin as a prognostic and therapeutic target in kidney fibrosis via a proteomic approach. Experimental & Molecular Medicine, 56(10), 2296-2308. https://doi.org/10.1038/s12276-024-01319-7

Unveiling the role of transgelin as a prognostic and therapeutic target in kidney fibrosis via a proteomic approach

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