Chronic intermittent hypoxia induces renal fibrosis through MR activation

• DOI: 10.1016/j.exger.2022.111780
• Publication Date: 2022-03-26T21:37:53Z
• Authors: Cui-juan Zhang; Hui Li; Yun-zhao Xiong; Yi Chang; Fan Yang; Xue-lian Ma; Xiang-ting Wang; Tatsuo Shimosawa; En-Sheng Ji; Qing-you Xu
• Keywords: Male; 0301 basic medicine; Sleep Apnea, Obstructive; Kidney; Fibrosis; Rats; 3. Good health; Disease Models, Animal; 03 medical and health sciences; Receptors, Mineralocorticoid; Animals; Humans; Kidney Failure, Chronic; Female; Renal Insufficiency, Chronic; Hypoxia

Obstructive sleep apnea syndrome (OSAS) is a disorder characterized by recurrent arousal from sleep and chronic intermittent hypoxia (CIH). OSAS-associated chronic kidney disease is mainly caused by CIH-induced tissue damage. Therefore, an OSAS model was established by CIH exposure in a hypoxic chamber for five weeks. In our study, macrophage infiltration and macrophage-myofibroblast transition (MMT) were observed in the kidneys of CIH rats and appeared to contribute to the development of renal fibrosis. However, the underlying mechanisms are not well defined. We also found that upon binding to the mineralocorticoid receptor (MR), aldosterone stimulated MMT and consequently led to renal fibrosis under hypoxic conditions. Additionally, an in vitro study of RAW264.7 macrophages demonstrated that MR activation may contribute to MMT, which resulted in a predominant M1 phenotype under hypoxic conditions. These effects were reversed by the MR blocker eplerenone. These results provide preliminary evidence that MR activation might be involved in the transdifferentiation of macrophages into myofibroblasts in the CIH model. The attenuation of renal injury demonstrates a protective role of MR blockade in CIH-induced renal disease.