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Published on: November 10, 2021
Inhibition of Renal Stellate Cell Activation Reduces Renal Fibrosis
Jin Joo Cha1, Chanchal Mandal2, Jung Yeon Ghee1
1Department of Nephrology, Korea University Ansan Hospital, Ansan 15355, Korea.
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.
Insights
Researchers identified renal stellate cells (RSCs) as kidney counterparts of liver stellate cells. A novel therapy, R-III, effectively inhibited RSC activation and reduced kidney fibrosis in mice.
Area of Science:
- Nephrology
- Cell Biology
- Fibrosis Research
Background:
- Interstitial fibrosis is a hallmark of chronic kidney disease, driven by myofibroblasts.
- Platelet-derived growth factor receptor-β (PDGFR-β)-positive mesenchymal cells are implicated as a primary source of these myofibroblasts.
- Previous work showed albumin and its derivative R-III inhibit hepatic stellate cell (HSC) activation and reduce liver fibrosis.
Purpose of the Study:
- To isolate and characterize renal stellate cells (RSCs) from rat kidney tissue.
- To investigate the potential of RSCs as therapeutic targets for kidney fibrosis.
- To evaluate the efficacy of R-III in treating kidney fibrosis.
Main Methods:
- RSCs were isolated from rat kidneys using an HSC protocol and characterized.
- In vitro studies assessed RSC transdifferentiation into myofibroblasts and the effect of albumin/R-III.
- Therapeutic effects of R-III were evaluated in a mouse model of unilateral ureteral obstruction (UUO)-induced renal fibrosis.
Main Results:
- RSCs exhibited characteristics similar to HSCs, including vitamin A storage and marker expression.
- RSCs spontaneously transdifferentiated into myofibroblasts in vitro, an effect inhibited by albumin or R-III.
- R-III treatment reduced renal fibrosis in UUO mice and localized to Cygb/STAP-positive cells.
Conclusions:
- Renal stellate cells (RSCs) are the functional equivalents of hepatic stellate cells in the kidney.
- RSCs are a promising therapeutic target for combating renal fibrosis.
- R-III demonstrates potential as an anti-fibrotic agent for kidney disease.
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