title: High density lipoprotein cholesterol promotes the proliferation of bone-derived mesenchymal stem cells via binding scavenger receptor-B type I and activation of PI3K/Akt, MAPK/ERK1/2 pathways.
abstract: High-density lipoprotein (HDL) possesses protective properties in cardiovascular diseases. However, the effect of HDL on the mesenchymal stem cells (MSCs), which could be mobilized to the damaged myocardial tissue, has not been well elucidated yet. In the current study, we investigated the effect of HDL on the proliferation of MSCs so as to reveal its molecular mechanisms. MSCs derived from rats were treated with HDL in different concentrations and for different periods. The proliferation of MSCs was measured with MTT and BrdU cell proliferation assay. The phosphorylation of Akt, ERK1/2 and the expression of p21 were evaluated by Western blotting. After the activity of respective pathways was down-regulated by the specific inhibitor and the gene of scavenger receptor-B type I (SR-BI) was knocked down by RNA interference, BrdU assay was performed to examine this effect of HDL on MSCs. We found that the proliferation of MSCs induced by HDL, in a time- and concentration-dependent manner, was the phosphorylation of Akt- and ERK1/2-dependent, which was significantly attenuated by the specific inhibitor to respective pathways. Moreover, MAPK/ERK1/2 pathway exerted a more dominating effect on this process. SR-BI contributed to HDL-induced proliferation of MSCs, which was effectively abolished by the silencing of SR-BI. The results suggested that HDL was capable of improving MSCs proliferation, in which MAPK/ERK1/2 and PI3K/Akt pathways involved and SR-BI played a critical role as well.
authors.affiliation: Department of Cardiology, Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
authors.forename: Jianfeng
authors.initials: J
authors.lastname: Xu
authors.forename: Juying
authors.initials: J
authors.lastname: Qian
authors.forename: Xinxing
authors.initials: X
authors.lastname: Xie
authors.forename: Li
authors.initials: L
authors.lastname: Lin
authors.forename: Jianying
authors.initials: J
authors.lastname: Ma
authors.forename: Zheyong
authors.initials: Z
authors.lastname: Huang
authors.forename: Mingqiang
authors.initials: M
authors.lastname: Fu
authors.forename: Yunzeng
authors.initials: Y
authors.lastname: Zou
authors.forename: Junbo
authors.initials: J
authors.lastname: Ge
mesh_terms: D000818:Animals; D001665:Binding Sites; D001854:Bone Marrow Cells / Q000166:cytology / Q000378:metabolism; D049109:Cell Proliferation; D008076:Cholesterol, HDL / Q000378:metabolism* / Q000494:pharmacology; D020935:MAP Kinase Signaling System; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D034622:RNA Interference; D051381:Rats; D017207:Rats, Sprague-Dawley; D051122:Scavenger Receptors, Class B / Q000378:metabolism*; D014162:Transfection
chemical_list: D008076:Cholesterol, HDL; D051122:Scavenger Receptors, Class B; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt