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

Abstract

Chronic 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. Chronic kidney disease is caused by kidney fibrosis, where healthy kidney tissue becomes scar, affecting kidney function. This research aimed to find noninvasive signs of kidney fibrosis by studying proteins in human kidney cells and animal CKD models. They used mass spectrometry, a method to identify and quantify proteins, to find potential signs in the body fluids that could show kidney fibrosis without needing kidney biopsy. The study found that the protein TAGLN increases in kidney tissue and urine in CKD conditions, suggesting it could be a useful sign of kidney fibrosis. Further tests showed that blocking TAGLN could reduce kidney fibrosis, indicating its potential as a target for new treatments. The researchers conclude that TAGLN is a promising sign of kidney fibrosis and could lead to better diagnostic and treatment options for CKD patients. This summary was initially drafted using artificial intelligence, then revised and fact-checked by the author.