We explored whether platelet-derived growth factor (PDGF)-BB regulates corpus cavernosum smooth muscle cell gap junctions and can ameliorate erectile dysfunction and how it modulates connexin43 (CX43) after bilateral cavernous neurectomy. Primary cultured rat corpus cavernosum smooth muscle cells were treated with PDGF-BB with or without a PDGFR inhibitor, Akt siRNA or the depletion or promotion of β-catenin. PDGF-BB improved CCSMCs gap junction coupling and increased CX43 and PDGFRβ expression; inhibition of PDGFR activity down-regulated CX43 and decreased Akt and nuclear β-catenin. Knockdown or promotion of β-catenin down-regulated and up-regulated CX43 expression respectively. Moreover, β-catenin activation induced CX43 nuclear accumulation, which impeded CX43 down-regulation induced by PDGFR inhibition, suggesting that CX43 expression is positively correlated with nuclear β-catenin expression. Furthermore, CX43 promoter luciferase and chromatin immunoprecipitation assays indicated that β-catenin regulates CX43 transcription by directly interacting with its promoter. Male rats underwent bilateral cavernous neurectomy. After 12 weeks, they were injected with PDGF-BB, CX43 and PDGFRβ expression was significantly lower than in the control group, which was reversed by PDGF-BB injection. These results suggested that PDGF-BB contributed to the improvement of gap junction intracellular communication among corpus cavernosum smooth muscle cells, increased CX43 through PDGFRβ/Akt/nuclear β-catenin signalling, and ameliorated cavernous nerve injury-induced erectile dysfunction.
Keywords: bilateral cavernous neurectomy; connexin43; erectile dysfunction; gap junction; platelet-derived growth factor-BB.
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