Journal
EXPERIMENTAL CELL RESEARCH
Volume 362, Issue 2, Pages 252-259Publisher
ELSEVIER INC
DOI: 10.1016/j.yexcr.2017.11.025
Keywords
Erectile dysfunction; Platelet-derived growth factor; Connexin 43; PI3K; AKT; beta-catenin
Categories
Funding
- National Natural Science Foundation of China [81571431, 81603620]
- Zhejiang Provincial Natural Science Foundation of China [LY15H040010]
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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 cavemosum 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), beta-catenin, and Cx43, whereas inhibition of PDGFR or activation of phosphatidylinositol 3 kinase (PI3K)/AKT signaling altered beta-catenin and Cx43 expression. Meanwhile, silencing beta-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/beta-catenin signaling and ultimately affecting GJ function in ED. Thus, targeting this pathway is a potential therapeutic strategy for the treatment of ED.
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