Renal IGFBP6 Interacts With THBS1 to Drive Renal Cellular Senescence and Fibrosis
Year: 2026
Type: article
Abstract: Epithelial dedifferentiation and myofibroblast activation are critical drivers of chronic kidney disease (CKD) progression. Elevated levels of IGFBP6 have been linked to decreased renal function in CKD patients, but its precise role and underlying mechanisms remain unclear. In this study, we observed significantly increased IGFBP6 expression in the kidney tissues of both renal fibrosis patients and animal models. Global or tubule-specific IGFBP6 knockout attenuated renal cellular senescence and fibrosis development in mice. In vitro, IGFBP6 deficiency preserved epithelial cell phenotype and inhibited fibroblast activation. Additionally, anti-IGFBP6 treatment demonstrated promising therapeutic effects in alleviating renal cellular senescence and fibrosis. Mechanistically, IGFBP6, acting as an adaptor protein, could bind to thrombospondin 1 (THBS1) and prevent its ubiquitination-mediated degradation, thereby activating the THBS1-CD47 cellular pathway in epithelial cells, which contributed to renal cellular senescence and fibrosis. Notably, both genetic and neutralizing antibody-mediated inhibition of IGFBP6 alleviated renal cellular senescence and fibrosis, suggesting that the IGFBP6/THBS1/CD47 axis represents a potential therapeutic target for chronic kidney injury.
Source: Advanced Science
DOI: 10.1002/advs.75802
Authors: Ju‐tao Yu, Chang‐geng Xu, Xiao‐wei Hu, Run‐run Shan, Jia‐nan Wang, Xiang‐yu Li, Yu‐qing Wang, Yu‐hang Dong, Shen‐Zhuo‐Fan Huang, Shuai Sun, Tian Zhao, Ya‐Xin Ru, Xiao‐yu Shen, Rui Hou, Jian‐min You, Fei Zhang, Chao Li, Jie Wei, Chao Hou, Zhi‐juan Wang, Dan‐feng Zhang, Juan Jin, Jia‐gen Wen, Yu‐jie Liu, Ming‐ming Liu, Xiao‐ming Meng, Wei Wang
Institutions: Anhui Medical University, Central Hospital of Wuhan, Huazhong University of Science and Technology, Anhui Provincial Children's Hospital, State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, First Affiliated Hospital of Anhui Medical University, University of Hong Kong, Second Affiliated Hospital of Anhui Medical University, University of Science and Technology of China
Language: English
Subfield: Nephrology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $6,730
OpenAlex ID: W7162135638