133b targeted 3'-UTR of the specificity protein 1 (SP1). ChIP assay demonstrated that SP1 can interact with the GC-rich region in the MYPT1 promoter and CPI-17 gene promoters were governed by the proximal GC-boxes, where SP1 transcription factors bound. Upregulation of miR-133b could down-regulate the expression of SP1, dramatically revert HG-induced phosphorylation level of MYPT1 at The853 of MLCP and CPI-17 at Thr38. In vivo experiment exhibited erectile function in miR-133b agomir group was markedly increased in the diabetic rats compared with the negative control groups and diabetic ED group. Mechanistically, consistented with in vitro experiments, miR-133b supplementation induced relaxation of the CCSM via nitric oxide-independent pathways.CONCLUSIONS: Three miRs were found in diabetic ED rat model. The present results indicate that miR-133b supplementation could improve erectile function in diabetic ED rats probably by regulating the contractility of CCSM via myosin light chain phosphatase inhibition.
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