| First Author | Wang X | Year | 2022 |
| Journal | Front Immunol | Volume | 13 |
| Pages | 864984 | PubMed ID | 35585990 |
| Mgi Jnum | J:338864 | Mgi Id | MGI:7279639 |
| Doi | 10.3389/fimmu.2022.864984 | Citation | Wang X, et al. (2022) MicroRNA-382 Promotes M2-Like Macrophage via the SIRP-alpha/STAT3 Signaling Pathway in Aristolochic Acid-Induced Renal Fibrosis. Front Immunol 13:864984 |
| abstractText | Aristolochic acid nephropathy (AAN) is a type of drug-induced nephropathy and is correlated with a potentially progression of kidney fibrosis. However, whether miR-382 is implicated in macrophage activation in AA-induced kidney fibrosis remains elusive. Here, cell-sorting experiments defined a significant miR-382 enrichment in renal macrophage after AAN 14 days. Then, we found that treatment of AA induced a significant switch in the phenotype of macrophage both in vivo and in vitro. Furthermore, miR-382 knockout (KO) mice and miR-382(-/-) bone marrow-derived macrophage (BMDM) were subjected to AA induction. We found that both systemic KO and macrophage-specific miR-382 depletion notably suppressed M2-like macrophage activation as well as kidney interstitial fibrosis. Additionally, adoptive transfer of miR-382 overexpression BMDMs into mice promoted AA-induced kidney injury. Moreover, in cultured macrophage, upregulation of miR-382 promoted M2-related gene expression, accompanied by downregulation of signal regulatory protein alpha (SIRP-alpha) and activation of signal transducer and activator of transcription 3 (STAT3). The interaction between miR-382 and SIRP-alpha was evaluated via dual-luciferase assay. Knockdown of SIRP-alpha upregulated phosphorylated STAT3 at S727 and Y705. Pharmacological inhibition of STAT3 was performed both in vivo and in vitro. Inhibition of STAT3 attenuated AA-induced kidney fibrosis, in parallel to lesser macrophage M2 polarization. Coculture experiments further confirmed that overexpressed miR-382 in macrophage promoted injuries of tubular cells. Luminex bio-chip detection suggested that IL-4 and CCL-5 were critical in the cross talk between macrophages and tubular cells. Taken together, our data suggest that miR-382 is a critical mediator in M2-like macrophage polarization and can be a promising therapeutic target for kidney fibrosis. |
