Inhibition of Renal Stellate Cell Activation Reduces Renal Fibrosis.

Abstract

Interstitial fibrosis is a common feature of chronic kidney disease, and platelet-derived growth factor receptor-β (PDGFR-β)-positive mesenchymal cells are reportedly the major source of scar-producing myofibroblasts. We had previously demonstrated that albumin and its derivative R-III (a retinol-binding protein-albumin domain III fusion protein) inhibited the transdifferentiation/activation of hepatic stellate cells (HSCs) to myofibroblasts and that R-III administration reduced liver fibrosis. In this study, we isolated cells (referred to as renal stellate cells, RSCs) from rat kidney tissues using the HSC isolation protocol and compared their morphological and biochemical characteristics with those of HSCs. RSCs shared many characteristics with HSCs, such as storage of vitamin A-containing lipid droplets and expression of HSC markers as well as pericyte markers. RSCs underwent spontaneous transdifferentiation into myofibroblasts in in vitro culture, which was inhibited by albumin expression or R-III treatment. We also evaluated the therapeutic effects of R-III in unilateral ureteral obstruction (UUO)-induced renal fibrosis in mice. Injected R-III localized predominantly in cytoglobin/stellate cell activation-associated protein (Cygb/STAP)-positive cells in the kidney and reduced renal fibrosis. These findings suggest that RSCs can be recognized as the renal counterparts of HSCs and that RSCs represent an attractive therapeutic target for anti-fibrotic therapy.

• Authors: Jin Joo Cha, Chanchal Mandal, Jung Yeon Ghee, Ji Ae Yoo, Mi Jin Lee, Young Sun Kang, Young Youl Hyun, Ji Eun Lee, Hyun Wook Kim, Sang Youb Han, Jee Young Han, Ah Young Chung, Dae Wui Yoon, Im Joo Rhyu, Junseo Oh, Dae Ryong Cha
• Journal: Biomedicines (Biomedicines) Vol. 8 Issue 10 (Oct 19 2020) ISSN: 2227-9059 [Print] Switzerland
• PMID: 33086608 (Publication Type: Journal Article)