title: Ursolic acid induced anti-proliferation effects in rat primary vascular smooth muscle cells is associated with inhibition of microRNA-21 and subsequent PTEN/PI3K.
abstract: This study focused on the anti-proliferation effects of ursolic acid (UA) in rat primary vascular smooth muscle cells (VSMCs) and investigated underlying molecular mechanism of action. Rat primary VSMCs were pretreated with UA (10, 20 or 30μM) or amino guanidine (AG, 50μM) for 12h or with PI3K inhibitor LY294002 for 30min or with Akt inhibitor MK2206 for 24h, then 10% fetal bovine serum was used to induce proliferation. CCK-8 was used to assess cell proliferation. To explore the mechanism, cells were treated with UA (10, 20 or 30μM), LY294002 or MK2206, or transient transfected to inhibit miRNA-21 (miRNA-21) or to overexpress PTEN, then quantitative real-time PCR was used to assess the mRNA levels of miRNA-21 and phosphatase and tensin homolog (PTEN) for cells treated with UA or miRNA-21 inhibitor; western blotting was used to measure the protein levels of PTEN and PI3K. UA exerted significant anti-proliferation effects in rat primary VSMCs. Furthermore, UA inhibited the expression of miRNA-21 and subsequently enhanced the expression of PTEN. PTEN was found to inhibit the expression of PI3K. In conclusion, UA exerts anti-proliferation effects in rat primary VSMCs, which is associated with the inhibition of miRNA-21 expression and modulation of PTEN/PI3K signaling pathway.
authors.affiliation: Qingdao University Medical College, 308 Ningxia Road, Qingdao, Shandong, China.
authors.forename: Qixiao
authors.initials: Q
authors.lastname: Jiang
authors.affiliation: Qingdao University Medical College, 308 Ningxia Road, Qingdao, Shandong, China.
authors.forename: Yantao
authors.initials: Y
authors.lastname: Han
authors.affiliation: Qingdao University Medical College, 308 Ningxia Road, Qingdao, Shandong, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Gao
authors.affiliation: Qingdao University Medical College, 308 Ningxia Road, Qingdao, Shandong, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Tian
authors.affiliation: The Affiliated Hospital of Qingdao University, 16 Jiangsu Road, Qingdao, Shandong, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Li
authors.affiliation: Qingdao University Medical College, 308 Ningxia Road, Qingdao, Shandong, China. Electronic address: cbwang666@126.com.
authors.forename: Chunbo
authors.initials: C
authors.lastname: Wang
mesh_terms: D000818:Animals; D050197:Atherosclerosis / Q000188:drug therapy; D049109:Cell Proliferation / Q000187:drug effects; D002867:Chromones / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006575:Heterocyclic Compounds, 3-Ring / Q000494:pharmacology; D008297:Male; D035683:MicroRNAs / Q000037:antagonists & inhibitors* / Q000235:genetics; D009025:Morpholines / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000166:cytology*; D051059:PTEN Phosphohydrolase / Q000037:antagonists & inhibitors* / Q000235:genetics; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects; D014315:Triterpenes / Q000494:pharmacology* / Q000627:therapeutic use; D000097245:Ursolic Acid
chemical_list: D002867:Chromones; D006575:Heterocyclic Compounds, 3-Ring; D035683:MicroRNAs; D009025:Morpholines; D051059:PTEN Phosphohydrolase; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D014315:Triterpenes; D000097245:Ursolic Acid; C548887:MK 2206; C546082:mirn21 microRNA, rat; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; C487216:Pten protein, rat
keywords: Aminoguanidine hydrochloride (PubChem CID: 2734687); Anti-proliferation; LY294002 (PubChem CID: 3973); MK2206 (PubChem CID: 46930998); MicroRNA-21; PTEN/PI3K; Rat primary vascular smooth muscle cells; Ursolic acid; Ursolic acid (PubChem CID: 64945)