Lin Xie1, Lili Fu2, Changlin Mei2, Yi Wang1, Min Chen1, Xiangchen Gu1. 1. Department of Nephrology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine Shanghai 200437, China. 2. Department of Nephrology, Changzheng Hospital Shanghai 200001, China.
Abstract
BACKGROUND/AIMS: Icariin plays an antifibrotic role in the unilateral ureteral obstruction (UUO) model; however, its primary mechanism has not been elucidated. G protein-coupled estrogen receptor (GPER) has been shown to be associated with fibrosis and mitochondrial biogenesis. In this study, we aimed to investigate the impact of GPER on renal fibrosis and whether icariin attenuates renal fibrosis dependent on GPER. METHODS: In the in vivo study, 10-week-old mice were subjected to the UUO model followed by UUO with icariin, G-15 (a GPER antagonist), and icariin + G-15. GPER expression, renal fibrosis levels, and mitochondrial alterations were measured and analyzed. In an in vitro study, we examined the antifibrotic effect of icariin on rat renal fibroblasts (NRK-49F) via GPER. RESULTS: Consistent with a previous study, icariin significantly attenuated fibrotic markers and protected the kidneys against mitochondrial injuries in the UUO model. However, G-15 exacerbated renal fibrosis and abolished the protective effect of icariin in the UUO model. Furthermore, antagonizing or knocking down GPER in NRK-49F significantly increased fibrotic markers and eliminated the antifibrotic effect of icariin. CONCLUSIONS: Our findings indicate that (1) GPER inhibition exacerbates renal fibrosis, and (2) icariin exerts antifibrotic effects against renal fibrosis through GPER. AJTR
BACKGROUND/AIMS: Icariin plays an antifibrotic role in the unilateral ureteral obstruction (UUO) model; however, its primary mechanism has not been elucidated. G protein-coupled estrogen receptor (GPER) has been shown to be associated with fibrosis and mitochondrial biogenesis. In this study, we aimed to investigate the impact of GPER on renal fibrosis and whether icariin attenuates renal fibrosis dependent on GPER. METHODS: In the in vivo study, 10-week-old mice were subjected to the UUO model followed by UUO with icariin, G-15 (a GPER antagonist), and icariin + G-15. GPER expression, renal fibrosis levels, and mitochondrial alterations were measured and analyzed. In an in vitro study, we examined the antifibrotic effect of icariin on rat renal fibroblasts (NRK-49F) via GPER. RESULTS: Consistent with a previous study, icariin significantly attenuated fibrotic markers and protected the kidneys against mitochondrial injuries in the UUO model. However, G-15 exacerbated renal fibrosis and abolished the protective effect of icariin in the UUO model. Furthermore, antagonizing or knocking down GPER in NRK-49F significantly increased fibrotic markers and eliminated the antifibrotic effect of icariin. CONCLUSIONS: Our findings indicate that (1) GPER inhibition exacerbates renal fibrosis, and (2) icariin exerts antifibrotic effects against renal fibrosis through GPER. AJTR
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