期刊
INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE
卷 51, 期 1, 页码 -出版社
SPANDIDOS PUBL LTD
DOI: 10.3892/ijmm.2022.5209
关键词
cyclophilin B; mitotic clonal expansion; adipogenesis; obesity; AKT; mTOR signaling pathway
This study investigated the role of CypB in 3T3-L1 adipocyte differentiation and found that CypB expression increased during differentiation. Knockdown of CypB delayed cell cycle progression and inhibited adipogenic transcription factors, while overexpression of CypB enhanced cell cycle progression and adipogenic transcription factors. CypB downregulated the expression of CHOP, suggesting an important physiological regulatory role in adipocyte differentiation.
Cyclophilin is known to act as a molecular chaperone in the endoplasmic reticulum. Recent studies have reported that the expression of cyclophilin B (CypB) is increased in ob/ob mice and its inhibitor suppresses adipocyte differentiation. However, the mechanism of action of CypB in adipocytes remains to be elucidated. The present study investigated the role of CypB in 3T3-L1 adipocyte differentiation. It showed that the expression level of CypB was increased during 3T3-L1 adipocyte differentiation by reverse transcription-quantitative PCR and western blotting analysis. CypB knockdown using short interfering RNA delayed cell cycle progression from the G(1)/S to G(2)/M phase through the mammalian target of rapamycin (mTOR) signaling pathway and inhibited the expression levels of adipogenic transcription factors including peroxisome proliferator-activated receptor gamma (PPAR gamma) and CCAAT-enhancer binding protein (C/EBP)alpha. Additionally, the accumulation of lipid droplets was inhibited by CypB knockdown. Conversely, overexpression of CypB promoted cell cycle progression from the G(1)/S to G(2)/M phase by the mTOR signaling pathway and enhanced the expression levels of adipogenic transcription factors including PPAR gamma and C/EBP alpha. Finally, the present study showed that CypB downregulated the expression of CHOP, a well-known negative regulator of adipogenesis. Taken together, the data suggested that CypB might serve important physiological regulatory roles in 3T3-L1 adipocyte differentiation.
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