MicroRNA-141 Inhibits the Proliferation of Penile Cavernous Smooth Muscle Cells Associated with Down-Regulation of the Rhoa/Rho Kinase Signaling Pathway

Background/Aims: The role of the RhoA/Rho kinase signaling pathway in diabetes mellitus-induced erectile dysfunction has been partially understood. Methods: In the present study, we explored the changes of the RhoA/Rho associated kinase (ROCK) signaling pathway in diabetic erectile dysfunction in vivo and the effects of microRNA-141 on the RhoA/ROCK signaling pathway in vitro. Results: The mRNA and protein expressions of RhoA and ROCK2 were significantly increased while the expression of microRNA-141 was decreased in the penile cavernous smooth muscle cells of rats with diabetic erectile dysfunction. Moreover, increased expression of microRNA-141, decreased expressions of RhoA and ROCK2 (mRNA and protein), accelerated cell proliferation rate and reduced cell apoptosis were found in the microRNA-141 mimics group and the siRNA-Rho group. The microRNA-141 expression in the microRNA-141 inhibitors + siRNA-Rho group was significantly decreased. microRNA-141 specifically bound to Rho-3’-UTR and down-regulated the expression of Rho gene at the post transcriptional level. Conclusion: Decreased expression of miR-141 is associated with up-regulation of RhoA and ROCK2 in the RhoA/ROCK signaling pathway in rats with diabetic erectile dysfunction. miR-141 inhibits the growth of penile cavernous smooth muscle cells associated with down-regulation of the RhoA/ROCK signaling pathway in vitro.

Effect of an Ethanol Extract ofScutellaria baicalensison Relaxation in Corpus Cavernosum Smooth Muscle

Aims of study. The aim of the present study was to investigate whether an ethanol extract ofScutellaria baicalensis(ESB) relaxes penile corpus cavernosum muscle in organ bath experiments.Materials and methods. Changes in tension of cavernous smooth muscle strips were determined by penile strip chamber model and in penile perfusion model. Isolated endothelium-intact rabbit corpus cavernosum was precontracted with phenylephrine (PE) and then treated with ESB.Results. ESB relaxed penile smooth muscle in a dose-dependent manner, and this was inhibited by pre-treatment with NG-nitro-l-arginine methyl ester (l-NAME), a nitric oxide (NO) synthase inhibitor, and 1H-[1, 2, 4]-oxadiazolo-[4,3-α]-quinoxalin-1-one (ODQ), a soluble guanylyl cyclase (sGC) inhibitor. ESB-induced relaxation was significantly attenuated by pretreatment with tetraethylammonium (TEA), a nonselective K+channel blocker, and charybdotoxin, a selective Ca2+-dependent K+channel inhibitor. ESB increased the cGMP levels of rabbit corpus cavernosum in a concentration-dependent manner without changes in cAMP levels. In a perfusion model of penile tissue, ESB also relaxed penile corpus cavernosum smooth muscle in a dose-dependent manner.Conclusion. Taken together, these results suggest that ESB relaxed rabbit cavernous smooth muscle via the NO/cGMP system and Ca2+-sensitive K+channels in the corpus cavernosum.