title: Downregulated microRNA-32 expression induced by high glucose inhibits cell cycle progression via PTEN upregulation and Akt inactivation in bone marrow-derived mesenchymal stem cells.
abstract: MicroRNAs regulate a host of physiological and pathological processes in mesenchymal stem cells (MSCs), although no published studies describe changes in microRNA expression or function in MSCs under in vitro hyperglycemic conditions. By using a microRNA microarray approach, we have identified that miRNA-32-5p expression is significantly reduced under hyperglycemic conditions in rat bone marrow-derived MSCs. Expression of miRNA-32-5p targets the 3'-untranslated region of the mRNA encoding phosphatase and tensin homologs deleted on chromosome 10 (PTEN), a negative regulator of the phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway. Exposure to high glucose levels reduced miR-32-5p expression, induced PTEN expression, and inhibited activation of the PI3K/Akt signaling pathway of MSCs. Conversely, overexpression of miR-32-5p inhibited the expression of PTEN, ameliorated the inhibitory effect of high glucose levels on the PI3K/Akt signaling pathway, and promoted cell cycle progression from G0/G1 to G2/M and S phases. Our study indicates that exposure of MSCs to hyperglycemic conditions reduces miR-32-5p expression and disturbs cell cycle progression through a PTEN-mediated inhibitory effect on the PI3K/Akt signaling pathway. In summary, MiR-32-5p is a potentially important therapeutic agent for preventing MSC dysfunction under hyperglycemic conditions.
authors.affiliation: Department of Burn and Plastic Surgery, Burns Institute, First Hospital Affiliated to General Hospital of PLA, Beijing, People's Republic of China.
authors.forename: Guiying
authors.initials: G
authors.lastname: Zhu
authors.forename: Jiake
authors.initials: J
authors.lastname: Chai
authors.forename: Li
authors.initials: L
authors.lastname: Ma
authors.forename: Hongjie
authors.initials: H
authors.lastname: Duan
authors.forename: Haijun
authors.initials: H
authors.lastname: Zhang
mesh_terms: D020413:3' Untranslated Regions; D000818:Animals; D015153:Blotting, Western; D001853:Bone Marrow / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects*; D002478:Cells, Cultured; D019295:Computational Biology / Q000379:methods; D015536:Down-Regulation; D004789:Enzyme Activation; D005947:Glucose / Q000494:pharmacology*; D006943:Hyperglycemia / Q000378:metabolism / Q000473:pathology; D059630:Mesenchymal Stem Cells / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D009841:Oligonucleotides / Q000378:metabolism; D051059:PTEN Phosphohydrolase / Q000235:genetics / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D015398:Signal Transduction; D014162:Transfection; D015854:Up-Regulation
chemical_list: D020413:3' Untranslated Regions; D035683:MicroRNAs; D009841:Oligonucleotides; D012333:RNA, Messenger; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D051059:PTEN Phosphohydrolase; C487216:Pten protein, rat; D005947:Glucose