醛固酮诱导的MR/CSF1途径在肾炎性损伤中成纤维细胞向巨噬细胞样细胞转化

IF 5.2 2区医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL

Life sciences Pub Date : 2025-04-09 DOI:10.1016/j.lfs.2025.123627

Ruyan Lv , Ziqian Liu , Haixia Guo , Boya Zhang , Xuan Wang , Yunsong Peng , Yi Chang , Fan Yang , Yunzhao Xiong , Juan Hao , Xiaomeng Gao , Xiangting Wang , Qingyou Xu , Tatsuo Shimosawa , Panpan Qiang

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引用次数: 0

摘要

目的炎症性损伤促进慢性肾脏疾病（CKD）的进展，肾巨噬细胞的积累和增殖是炎症性损伤的典型表现。我们的目的是验证成纤维细胞向巨噬细胞样细胞转化是参与肾脏炎症损伤的巨噬细胞的新来源。材料与方法将swistar大鼠分为Sham组、ALD组（醛固酮输注12周）和ESA组（醛固酮和依沙塞隆通过饮食输注12周）。体外培养大鼠肾间质成纤维细胞（RKF），醛固酮或CSF1诱导，拮抗剂处理。流式细胞术和免疫荧光染色检测FSP-1+ F4/80+细胞在大鼠肾脏和RKF中的比例，包括M1标记物iNOS/CD86和M2标记物CD206/CD163。采用单细胞RNA测序法评估大鼠肾脏巨噬细胞的来源及相关基因表达。此外，利用免疫荧光检测CKD患者肾活检样本中的FSP-1+ F4/80+细胞。主要发现：在醛固酮输注大鼠和体外醛固酮处理的RKF肾脏中均观察到成纤维细胞向巨噬细胞样细胞的转变，并以M1表型为主分化。这种转化是通过MR/CSF1信号通路介导的，揭示了巨噬细胞的新来源，并为器官纤维化的机制提供了重要的见解。醛固酮通过MR/ CSF1通路诱导成纤维细胞向巨噬细胞样细胞转变。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

Fibroblast to macrophage-like cell transition in renal inflammatory injury through the MR/CSF1 pathway induced by aldosterone

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Fibroblast to macrophage-like cell transition in renal inflammatory injury through the MR/CSF1 pathway induced by aldosterone

Aims

Inflammatory injury promotes the chronic kidney disease (CKD) progression，with renal macrophage accumulation and proliferation of as typical manifestations of inflammatory injury. We aimed to verify fibroblast to macrophage-like cell transition as a new source of macrophages that participate in renal inflammatory injury.

Materials and methods

Wistar rats were divided into Sham, ALD (aldosterone infusion for 12 weeks), and ESA (aldosterone infusion and esaxerenone by diet for 12 weeks) groups. Rat kidney interstitial fibroblast (RKF) were cultured, induced with aldosterone or CSF1, and treated with antagonists in vitro. The proportions of FSP-1⁺ F4/80⁺ cells in the rat kidney and RKF, including M1 marker iNOS/CD86 and M2 marker CD206/CD163 were assessed by flow cytometry and immunofluorescence staining. Single-cell RNA sequencing was used to assess the origin of macrophages in the rat kidneys and related gene expression. Additionally, immunofluorescence was used to detect FSP-1⁺ F4/80⁺ cells in kidney biopsy samples from CKD patients.

Key findings

Fibroblast to macrophage-like cell transition was observed in both the kidneys of aldosterone-infused rats and in vitro aldosterone-treated RKF, with a predominant differentiation into the M1 phenotype. This transformation was mediated through the MR/CSF1 signalling pathway, revealing a novel source of macrophages and providing significant insights into the mechanisms underlying organ fibrosis.

Significance

Aldosterone induces fibroblast to macrophage-like cell transition through the MR/ CSF1 pathway.

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来源期刊

Life sciences 医学-药学

CiteScore

12.20

自引率

1.60%

发文量

841

审稿时长

6 months

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