GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE261nnn/GSE261069/primaryOK200GenomicsMus musculusNon-coding RNA profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE261069GEOGSEfalseBMAL1 regulates tubular epithelial-derived exosomal miR-27a-3p to inhibits macrophage-myofibroblast transition thus alleviating ischemia/reperfusion induced renal fibrosisExosomal microRNAs are closely related to the progression of renal fibrosis. The circadian rhythm gene BMAL1 is thought to be involved in a variety of diseases. However, how BMAL1 regulates renal fibrosis induced by ischemia-reperfusion injury (IRI) has not been determined. We first examined BMAL1 expression, exosomal expression, the macrophage-to-myofibroblast transition (MMT) ratio, and renal fibrosis levels in mice with renal IRI. The results showed that renal IRI induced a decrease in BMAL1 expression, along with an increase in exosome secretion, MMT formation and renal fibrosis. Next, we overexpressed BMAL1 in mouse kidneys and found that BMAL1 inhibited IRI-induced MMT and fibrosis. We confirmed that exosome-mediated MMT directly aggravated renal fibrosis and that this process was directly regulated by BMAL1 through in vivo and in vitro exosome uptake experiments and Rab27a knockout mouse construction. High-throughput miRNA sequencing of exosomes derived from TCMK-1 cells and ChIP assays were used to confirm that exosomal miR-27a-3p was downregulated after hypoxia-reoxygenation (H/R) treatment and that BMAL1 directly promoted the transcription of miR-27a-3p. We identified TGFBR1 as the target gene of miR-27a-3p by transfecting cells with miR-27a-3p mimics and miR-27a-3p inhibitors and performing dual luciferase assays. Finally, we transfected cells with si-TGFBR1 and identified the TGFBR1/smad3 pathway as a key pathway for regulating MMT and renal fibrosis regulated by tubular epithelium-derived exosomal miR-27a-3p. Our findings indicated that BMAL1 was suppressed in renal IRI, which promoted MMT and renal fibrosis by upregulating the level of miR-27a-3p in tubular epithelial-derived exosomes.2026/06/10GSE261069GSM8133630GSM8133632GSM8133631GSM8133634GSM8133633GSM8133635GSM8133627GSM8133629GSM813362824247261069Mus musculus[42244974]