PDGF-mediated PI3K/AKT/β-catenin signaling regulates gap junctions in corpus cavernosum smooth muscle cells
Journal Article
·
· Experimental Cell Research
- The Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou (China)
- Department of Urology, The Second Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou (China)
Highlights: • PDGFR expression is high in endothelial/smooth muscle cell co-cultures under hypoxia. • PDGF is secreted by vascular endothelial and corpus cavernosum smooth muscle cells. • Hypoxia increases connexin (Cx)43 level in corpus cavernosum smooth muscle cells. • PDGF enhances Cx43 expression under hypoxic conditions. • PDGF regulates Cx43 in corpus cavernosum smooth muscle cells via PI3K/AKT/β-catenin. Erectile dysfunction (ED) is the most common sexual disorder that men report to healthcare providers. Gap junctions (GJs) are thought to be responsible for synchronous shrinkage of corpus cavernosum smooth muscle cells (CCSMCs), and play thus an important role in the maintenance of an erection. Hypoxia has been suggested as a pathological mechanism underlying ED. Here we demonstrate that hypoxia increased the expression of platelet-derived growth factor (PDGF) and the main GJ component connexin (Cx)43 in CCSMCs. Inhibiting PDGF receptor (PDGFR) activity decreased Cx43 expression. Treatment with different concentrations of PDGF increased the levels of phosphorylated protein kinase B (AKT), β-catenin, and Cx43, whereas inhibition of PDGFR or activation of phosphatidylinositol 3 kinase (PI3K)/AKT signaling altered β-catenin and Cx43 expression. Meanwhile, silencing β-catenin resulted in the downregulation of Cx43. These results demonstrate that PDGF secretion by CCSMCs and vascular endothelial cells is enhanced under hypoxic conditions, leading to increased Cx43 expression through PI3K/AKT/β-catenin signaling and ultimately affecting GJ function in ED. Thus, targeting this pathway is a potential therapeutic strategy for the treatment of ED.
- OSTI ID:
- 23082510
- Journal Information:
- Experimental Cell Research, Journal Name: Experimental Cell Research Journal Issue: 2 Vol. 362; ISSN 0014-4827; ISSN ECREAL
- Country of Publication:
- United States
- Language:
- English
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