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NLRP3 inflammasome mediates chronic intermittent hypoxia‐induced renal injury implication of the microRNA‐155/FOXO3a signaling pathway
Author(s) -
Wu Xu,
Chang Su Chi,
Jin Jifu,
Gu Wenyu,
Li Shanqun
Publication year - 2018
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.26784
Subject(s) - inflammasome , proinflammatory cytokine , oxidative stress , microbiology and biotechnology , inflammation , reactive oxygen species , signal transduction , endocrinology , medicine , chemistry , immunology , biology
Chronic intermittent hypoxia (CIH), as the foremost pathophysiological change of obstructive sleep apnea (OSA), contributes to continued deterioration in renal function. Nucleotide‐binding domain like receptor protein 3 (NLRP3) inflammasome is a multiprotein complex that triggers innate immune responses to infection and cell stress through activation of caspase‐1 and maturation of inflammatory pro‐interleukin‐1β cytokine. Emerging evidence indicates that inhibition of the NLRP3 inflammasome ameliorates renal injury. Nevertheless, it is uncertain whether NLRP3 inflammasome participates in CIH‐induced renal injury. The molecular mechanisms modulating NLRP3 inammasome activation remain to be elucidated. Compared with wild‐type mice, NLRP3 knockout mice dramatically protected them from kidney injury, as indicated by the restoration of creatinine levels, lessened histopathological alterations, and the suppression of macrophages inltration stained with F4/80. NLRP3 deciency notably reversed CIH‐induced oxidative stress (malondialdehyde and superoxide dismutase), concomitantly with the abrogated apoptosis‐related proteins and proinflammatory signaling pathway. Consistently, NLRP3‐decient tubular cells remarkably inhibited reactive oxygen species generation and NLRP3 inammasome activation. Furthermore, our study revealed that microRNA‐155 (miR‐155) was augmented in the renal tissue and HK‐2 cells exposed to CIH. In addition, we investigated the role of miR‐155 in the regulation of NLRP3 inammasome. Inhibition of miR‐155 suppressed the CIH‐induced NLRP3 inammasome activation in renal tubular cells, whereas overexpression of miR‐155 promoted oxidation and enhanced NLRP3 pathway. Collectively, we demonstrated that miR‐155 might be a positive‐regulator of NLRP3 pathway by inhibiting the targeted FOXO3a gene. These results established a link between the miR‐155/FOXO3a pathway and the NLRP3 inammasome, suggesting pharmacological blockage of NLRP3 as a potential therapeutic strategy for OSA‐associated chronic kidney disease.