ADSC Exosomes Mediate lncRNA-MIAT Alleviation of Endometrial Fibrosis by Regulating miR-150-5p

Abstract

BackgroundSecondary infertility remains a major complication of endometrial fibrosis in women. The use of exosomes from adipose-derived mesenchymal stem cells (ADSCs) has shown promising results for the treatment of endometrial fibrosis. However, the mechanisms of action of ADSC-exosome (ADSC-Exo) therapy remain unclear.Materials and MethodsAn endometrial fibrosis model was established in mice treated with alcohol and endometrial epithelial cells (ESCs) treated with TGF-β1. ADSCs were isolated from Sprague Dawley (SD) rats, and exosomes were isolated from ADSCs using ExoQuick reagent. Exosomes were identified by transmission electron microscopy (TEM), NanoSight, and Western blot analysis. The expression level of lncRNA-MIAT was detected by qPCR analysis. Western blot analysis was carried out to determine the protein levels of fibrosis markers (TGFβR1, α-SMA, and CK19). A dual-luciferase reporter gene assay was used to verify the relationship between target genes. The endometrial tissues of the endometrial fibrosis model were stained with HE and Masson’s trichrome.ResultsADSCs and ADSC-Exos were successfully isolated, and the expression level of lncRNA-MIAT was significantly down-regulated in endometrial tissue and the TGF-β1-induced ESC injury model, whereas ADSC-Exos increased the expression of lncRNA-MIAT in the TGF-β1-induced ESC model. Functionally, ADSC-Exo treatment repressed endometrial fibrosis in vivo and in vitro by decreasing the expression of hepatic fibrosis markers (α-SMA and TGFβR1) and increasing the expression of CK19. Moreover, miR-150-5p expression was repressed by lncRNA-MIAT in the TGF-β1-induced ESC injury model. The miR-150-5p mimic promoted TGF-β1-induced ESC fibrosis.ConclusionADSC-Exos mediate lncRNA-MIAT alleviation of endometrial fibrosis by regulating miR-150-5p, which suggests that lncRNA-MIAT from ADSC-Exos may be a viable treatment for endometrial fibrosis.

Transplantation of adipose-derived stem cells ameliorates Echinococcus multilocularis-induced liver fibrosis in mice

“…Fibrosis is a histological hallmark of Alveolar echinococcosis (AE), which may result in impaired architectonics of the parenchyma or the death of the metacestode [30]. Studies have evaluated the effects of ADSCs on fibrosis in animal models or cells [31][32][33]. Shen et al [34] showed that exosomal miR-19a from ADSCs inhibits TGF-β/Smad3 and p53 pathways by down-regulating HIPK2 levels, decreasing cell viability, and promoting ECM degradation, as well as by inhibiting the differentiation of corneal keratinocytes into myofibroblasts.…”

Expression profiles of long non-coding RNAs in neurogenic bladder of spinal cord injured rats: a transcriptomic analysis

“…In addition, the Miat/miR-133a-3p axis may be related to atrial fibrillationinduced myocardial fibrosis (22). The lncRNA Miat also improved endometrial fibrosis by targeting miR-150 and ameliorating fibrosis in diabetic nephropathy by regulating the expression of miR-147a and E2F3 (21,23). In this study, we found that lncRNA Miat was expressed at low levels in SCI rat bladder tissue.…”

Downregulation of lncRNA Miat contributes to the protective effect of electroacupuncture against myocardial fibrosis

“…For example, knockdown Miat could up-regulate the miRNA-24 expression and reduce the expression of TGF-β1 [ 78 ]. There are three binding sites of miRNA-150 in Miat, and Miat can regulate the expression of P300 through competitive binding with miRNA-150, thus regulating the occurrence of isoprenaline-induced cardiac hypertrophy [ 79 ]. Previous reports have found that Miat can sponge miRNA-133a-3p [ 55 ].…”