Apelin-induced vascular smooth muscle cell proliferation: the regulation of cyclin D1.
Apelin is the endogenous ligand of the G protein-coupled receptor, APJ. Vascular smooth muscle cells express both apelin and APJ, which are important regulatory factors in the cardiovascular and nervous systems. Importantly, APJ is also involved in the pathogenesis if HIV-1 infection. We investigated whether vascular smooth muscle cell proliferation was regulated through an apelin-pERK1/2-cyclin D1 signal transduction pathway. Apelin-13 significantly stimulated vascular smooth muscle cell proliferation and increased cell cycle progression. Apelin-13 a decreased the proportion of cell in the G0/G1 phase while increasing the number of cells in S phase. Apelin-13 also increased the levels of cyclin D1, cyclin E and pERK1/2. Treatment of cells with the MEK inhibitor PD98059 attenuated the apelin-3-induced pERK1/2 activation. Similarly, treatment with PD98059 partially diminished the apelin-13-induced expression of cyclin D1 and vascular smooth muscle cell proliferation. Taken together, these data established that apelin-13 stimulates vascular smooth muscle cell proliferation by promoting the G1-S phase transition, and that this effect is mediated in part by an apelin-pERK1/2-cyclin D1 signal cascade.
Institute of Pharmacology and Pharmacy, Nanhua University, Hengyang, China.
Feng
F
Li
Lanfang
L
Li
Xuping
X
Qin
Weinan
W
Pan
Fen
F
Feng
Feng
F
Chen
Bingyan
B
Zhu
Duanfang
D
Liao
Herbert
H
Tanowitz
Chris
C
Albanese
Linxi
L
Chen
D000818:Animals; D001013:Aorta, Thoracic / Q000166:cytology; D000073861:Apelin; D002352:Carrier Proteins / Q000494:pharmacology*; D018929:Cell Culture Techniques; D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects*; D002478:Cells, Cultured; D019938:Cyclin D1 / Q000502:physiology*; D005434:Flow Cytometry; D006801:Humans; D007239:Infections / Q000503:physiopathology; D036341:Intercellular Signaling Peptides and Proteins / Q000494:pharmacology; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley
D000073861:Apelin; C498579:Apln protein, rat; D002352:Carrier Proteins; D036341:Intercellular Signaling Peptides and Proteins; C495199:apelin-13 peptide; D019938:Cyclin D1