MicroRNA-143 regulates adipogenesis by modulating the MAP2K5-ERK5 signaling.
A better understanding of the molecular mechanisms that regulate adipose tissue-derived stromal cell (ADSC) differentiation could provide new insight into some adipose-tissue-related disease. The differentiation of ADSCs into adipocytes is a complex physiological process that includes clonal expansion, growth arrest, and terminal differentiation. Here the role of microRNA-143 (miR-143) during ADSC adipogenic differentiation was systematically investigated. We found that miR-143 expression was transiently decreased after adipogenic induction while increased from day 3 and peaked on day 7 after induction. We show for the first time that the role of miR-143 is not consistent in the differentiation process. The regulatory role depends on the differentiation stage that miR-143 acts on. When miR-143 is overexpressed during the clonal expansion stage, the adipogenic differentiation of ADSCs is inhibited, whereas the overexpression of miR-143 during the growth arrest stage or terminal differentiation stage promotes differentiation. Further we firstly demonstrate that miR-143 plays the modulational role by directly repressing MAP2K5, a key member of the MAPKK family in the MAPK signaling pathway. These findings suggest that miR-143 plays an important role in adipose tissue formation, with special implications for some metabolic disease in which the amount and/or function of adipose tissue is altered.
1] State Key Laboratory of Oral Diseases, Sichuan University, Chengdu 610044, P.R.China [2].
Lin
L
Chen
1] Department of Oral & Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, P.R.China [2].
Jia
J
Hou
Department of Oral & Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, P.R.China.
Lanfeng
L
Ye
Department of Oral & Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, P.R.China.
Yuanwei
Y
Chen
1] State Key Laboratory of Oral Diseases, Sichuan University, Chengdu 610044, P.R.China [2] Department of Oral & Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, P.R.China.
Junhui
J
Cui
Department of Oral & Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, P.R.China.
Weidong
W
Tian
State Key Laboratory of Oral Diseases, Sichuan University, Chengdu 610044, P.R.China.
Cai
C
Li
1] State Key Laboratory of Oral Diseases, Sichuan University, Chengdu 610044, P.R.China [2] Department of Oral & Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, P.R.China.
Lei
L
Liu
D050156:Adipogenesis / Q000502:physiology*; D000273:Adipose Tissue / Q000166:cytology* / Q000378:metabolism; D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D002453:Cell Cycle; D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D005260:Female; D048671:MAP Kinase Kinase 5 / Q000235:genetics / Q000378:metabolism*; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics*; D048054:Mitogen-Activated Protein Kinase 7 / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction
C569508:MIRN143 microRNA, rat; D035683:MicroRNAs; D012333:RNA, Messenger; D048054:Mitogen-Activated Protein Kinase 7; D048671:MAP Kinase Kinase 5; C482563:MAP2K5 protein, human