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MiR-146a-5p, targeting ErbB4, promotes 3T3-L1 preadipocyte differentiation through the ERK1/2/PPAR-γ signaling
Yifen Wang1, Jie Zhang1, Xueru Chu2
1Department of Infectious Disease, Qingdao Municipal Hospital, Qingdao University, 1 Jiaozhou Road, Qingdao, 266011, Shandong Province, China.
Background:
MicroRNAs (MiRNAs) are known to participate in preadipocyte differentiation, but the manner in which miR-146a-5p participates in this process remains unclear. This study was performed to examine the participation of miR-146a-5p in 3T3-L1 cell differentiation.
Material And Methods:
miR-146a-5p expression was upregulated and down-regulated to examine effects on 3T3-L1 cell differentiation. Bioinformatics analysis was performed to predict its target genes, and the signaling pathway it regulates was identified by qRT-PCR and Western blotting. The expression of miR-146a-5p in epididymal adipose tissue from obese mice and in an obese mouse adipose cell model was examined by qRT-PCR.
Results:
3T3-L1 cells differentiated into mature adipocytes successfully, as verified by increased areas of intracellular lipid droplets and elevated expression of mature adipocyte markers, and these cells had elevated miR-146a-5p expression. The intracellular lipid droplet and triglyceride contents and the expression of mature adipocyte markers were significantly increased in miR-146a-5p-overexpressing 3T3-L1 cells and markedly decreased in miR-146a-5p-inhibited 3T3-L1 cells. ErbB4 was a predicted target gene of miR-146a-5p. In miR-146a-5p-overexpressing 3T3-L1 cells, ErbB4 expression and ERK1/2 phosphorylation were decreased and the expression of PPAR-γ was increased; the opposite was observed in miR-146a-5p-inhibited 3T3-L1 cells. In addition, miR-146a-5p expression was significantly increased in the mouse epididymal adipose tissue and adipose cell model.
Conclusions:
Upregulated miR-146a-5p expression was related to 3T3-L1 cell differentiation. MiR-146a-5p promoted 3T3-L1 cell differentiation by targeting ErbB4 and via the ERK1/2/PPAR-γ signaling pathway.
Insights
MicroRNA-146a-5p (miR-146a-5p) promotes 3T3-L1 cell differentiation into adipocytes. This microRNA targets ErbB4 and influences the ERK1/2/PPAR-γ pathway, impacting fat cell development.
Area of Science:
- Molecular Biology
- Cell Biology
- Biochemistry
Background:
- MicroRNAs (MiRNAs) regulate adipocyte differentiation.
- The specific role of miR-146a-5p in this process is not fully understood.
Purpose of the Study:
- To investigate the role of miR-146a-5p in 3T3-L1 preadipocyte differentiation.
- To identify the molecular targets and signaling pathways regulated by miR-146a-5p.
Main Methods:
- 3T3-L1 cells were treated to upregulate or downregulate miR-146a-5p expression.
- Bioinformatics analysis predicted target genes.
- Quantitative real-time PCR (qRT-PCR) and Western blotting assessed gene and protein expression.
- Obese mouse adipose tissue and cell models were used to examine miR-146a-5p expression.
Main Results:
- miR-146a-5p expression increased during 3T3-L1 differentiation.
- Overexpression of miR-146a-5p enhanced adipocyte differentiation markers and lipid accumulation.
- Inhibition of miR-146a-5p reduced these differentiation markers.
- ErbB4 was identified as a direct target of miR-146a-5p.
- miR-146a-5p modulated the ERK1/2/PPAR-γ signaling pathway.
- miR-146a-5p expression was elevated in obese mouse adipose tissue and cell models.
Conclusions:
- miR-146a-5p promotes 3T3-L1 cell differentiation.
- This promotion occurs through targeting ErbB4 and modulating the ERK1/2/PPAR-γ signaling pathway.
- Increased miR-146a-5p expression is associated with obesity.
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