Death-associated protein kinase3 mediates vascular structural remodeling via stimulating smooth muscle cell proliferation and migration

Death-associated protein kinase (DAPK)3 also known as zipper-interacting kinase is a serine/threonine kinase that mainly regulates cell death and smooth muscle contraction. We previously found that protein expression of DAPK3 increases in mesenteric artery from spontaneously hypertensive rats (SHR) and that DAPK3 mediates the development of hypertension in SHR partly through promoting reactive oxygen species-dependent vascular inflammation. However, it remains to be clarified how DAPK3 controls smooth muscle cells (SMCs) proliferation and migration that are also important processes for the hypertension development. We therefore sought to reveal whether DAPK3 affects SMCs proliferation and migration. Small interfering RNA (siRNA) against DAPK3 significantly inhibited platelet-derived growth factor (PDGF)-BB-induced SMCs proliferation and migration as determined by bromodeoxyuridine incorporation and cell counting assay as well as boyden chamber assay, respectively. DAPK3 siRNA or a pharmacologic inhibitor of DAPK3 inhibited PDGF-BB-induced lamellipodia formation as determined by a rhodamine-phalloidin staining. DAPK3 siRNA or DAPK inhibitor significantly reduced PDGF-BB-induced activation of p38 and heat shock protein (HSP)27 as determined by Western blotting. In ex vivo, PDGF-BB-induced SMCs out-growth was significantly inhibited by DAPK inhibitor. In vivo, DAPK inhibitor significantly prevented carotid neointimal hyperplasia in mice ligation model. The present results for th...
Source: Clinical Science - Category: Biomedical Science Authors: Source Type: research