Prostacyclin Mitigates Renal Fibrosis by Activating Fibroblast Prostaglandin I2 Receptor

作者：Jing Li, Yi Guan, Yunyu Xu, Yingxue Cao, Qionghong Xie, Raymond C. Harris, Matthew D. Breyer, Limin Lü, Chuan‐Ming Hao · 发表于：Journal of the American Society of Nephrology · 年份：2023 · DOI：10.1681/asn.0000000000000286 · 被引用次数：7 · 研究领域：Inflammatory mediators and NSAID effects、Advanced Glycation End Products research、Acute Kidney Injury Research

SIGNIFICANCE STATEMENT: Renal fibrosis is a common pathologic process of progressive CKD. We have provided strong evidence that PGI 2 is an important component in the kidney injury/repairing process by reducing fibrosis and protecting renal function from declining. In our study, administration of a PGI 2 analog or selective PTGIR agonist after the acute injury ameliorated renal fibrosis. Our findings provide new insights into the role of PGI 2 in kidney biology and suggest that targeting PGI 2 /PTGIR may be a potential therapeutic strategy for CKD. BACKGROUND: Prostanoids have been demonstrated to be important modulators to maintain tissue homeostasis in response to physiologic or pathophysiologic stress. Prostacyclin (PGI 2 ) is a member of prostanoids. While limited studies have shown that PGI 2 is involved in the tissue injury/repairing process, its role in renal fibrosis and CKD progression requires further investigation. METHODS: Prostacyclin synthase ( Ptgis )-deficient mice, prostaglandin I 2 receptor ( Ptgir )-deficient mice, and an oral PGI 2 analog and selective PTGIR agonist were used to examine the role of PGI 2 in renal fibrosis in mouse models. We also analyzed the single-cell RNA-Seq data to examine the PTGIR -expressing cells in the kidneys of patients with CKD. RESULTS: Increased PTGIS expression has been observed in fibrotic kidneys in both humans and mice. Deletion of the PTGIS gene aggravated renal fibrosis and decline of renal function in murine models. A...