한빛사논문
Soie Kwon 1,2,3,15, Seongmin Cheon 4,15, Kyu-Hong Kim 5,6, Areum Seo 5, Eunjin Bae 7, Jae Wook Lee 8, Ran-Hui Cha 9, Jin Ho Hwang 1,2, Yong Chul Kim 10,11, Dong Ki Kim 10,11, Yon Su Kim 5,9,10,11, Dohyun Han 12,13,14,* and Seung-Hee Yang 5,9,*
1Department of Internal Medicine, Chung-Ang University Hospital, Seoul, Republic of Korea.
2Department of Internal Medicine, College of Medicine, Chung-Ang University, Seoul, Republic of Korea.
3Department of Clinical Medical Sciences, Seoul National University, Seoul, Republic of Korea.
4School of Biological Sciences and Technology, Chonnam National University, Gwangju, Republic of Korea.
5Kidney Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea.
6Department of Biomedical Sciences, College of Medicine, Seoul National University, Seoul, Republic of Korea.
7Department of Internal Medicine, Gyeongsang National University College of Medicine, Gyeongsang University Changwon Hospital, Gyeongsang, Republic of Korea.
8Nephrology Clinic, National Cancer Center of Korea, Seoul, Republic of Korea.
9Biomedical Research Institute, Seoul National University Hospital, Seoul, Republic of Korea.
10Department of Internal Medicine, Seoul National University Hospital, Seoul, Republic of Korea.
11Department of Internal Medicine, Seoul National University, College of Medicine, Seoul, Republic of Korea.
12Proteomics Core Facility, Biomedical Research Institute, Seoul National University Hospital, Seoul, Republic of Korea.
13Department of Transdisciplinary Medicine, Seoul National University Hospital, Seoul, Republic of Korea.
14Department of Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea.
15These authors contributed equally: Soie Kwon, Seongmin Cheon
*Corresponding authors: correspondence to Dohyun Han or Seung-Hee Yang
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.
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