Macrophages regulates the transition of pericyte to peritoneal fibrosis through the GSDMD/IL-1β axis

作者：Qiuyuan Shao, Cheng Sun, Qingyan Zhang, Jin Liu, Yangyang Xia, Bo Jin, Xiao-Ping Qian · 发表于：International Immunopharmacology · 年份：2021 · DOI：10.1016/j.intimp.2021.108323 · 被引用次数：9 · 研究领域：Dialysis and Renal Disease Management、Immune cells in cancer、Chronic Kidney Disease and Diabetes

BACKGROUND: End stage renal disease (ESRD) has caused public health problem with high prevalence worldwide. Peritoneum from peritoneal dialysis patients with ESRD can induce pathological changes of the peritoneum, including fibrosis. The trans-differentiation of pericytes has been found to be closely associated with inflammatory diseases, such as organ fibrosis. However, the function of macrophages in regulating the transition of pericyte to peritoneal fibrosis is unclear. METHODS: Histological examination was conducted using Hematoxylin and eosin (HE) staining and Masson's trichrome staining. The protein levels were determined via western blot. Enzyme-linked immunosorbent assay (ELISA) was used to examine IL-1β concentrations. Gasdermin D (GSDMD) was knocked out in mice by Clustered Regularly Interspaced Short Palindromic Repeats-CRISPR-Associated 9 (CRISPR-Cas9). RESULTS: Mice receiving dextrose peritoneal dialysate displayed mesothelial cell monolayer loss and thickness of submesothelial compact zone increase. Moreover, dextrose peritoneal dialysate treatment up-regulated GSDMD expression. GSDMD knockdown inhibited IL-1β production in macrophages. Further, pericytes were treated with cultural supernatant from macrophages. We found that GSDMD knockdown suppressed fibrosis and vascular endothelial growth factor (VEGF)/phosphoinositide 3-kinase (PI3K) pathway in pericytes. In addition, GSDMD were knocked out in mice using CRISPR/Cas9. The histological examinations revealed th...