Cysteine‐rich protein 61 regulates adipocyte differentiation from mesenchymal stem cells through mammalian target of rapamycin complex 1 and canonical Wnt signaling

Abstract

Emerging evidence suggests that cysteine-rich protein 61 (CYR61) plays a role in the differentiation and development of chondrocytes, osteoblasts, and osteoclasts; however, little is known about its role in adipogenesis. The current study indicates that the expression level of Cyr61 was altered in primary cultured marrow stromal cells and the established mesenchymal cell line, C3H10T1/2, after adipogenic treatment. Overexpressing Cyr61 repressed C3H10T1/2 and primary marrow stromal cells to differentiate into mature adipocytes. Conversely, inhibition of endogenous Cyr61 induced C3H10T1/2 and primary marrow stromal cells to fully differentiate. Mechanism investigations reveal that knockdown of Cyr61 inhibited the nuclear translocation of β-catenin and decreased nuclear protein levels of β-catenin and transcription factor 7-like 2. Moreover, the silencing of Cyr61 increased protein levels of phosphorylated ribosomal protein S6 kinase B1, mammalian target of rapamycin, eukaryotic translation initiation factor 4E-binding protein 1, and ribosomal protein S6-the major components of mammalian target of rapamycin complex 1 (mTORC1) signaling-in C3H10T1/2 cells. Additional investigations demonstrated that treatment with rapamycin significantly attenuated adipocyte formation that was induced by Cyr61 small interfering RNA (siRNA) transfection. Moreover, Cyr61 siRNA also lost its ability to stimulate adipocyte formation under the background of β-catenin overexpression. Taken together, our study provides evidence that CYR61 regulates adipocyte differentiation via multiple signaling pathways that involve at least the inactivation of mTORC1 signaling and the activation of canonical Wnt signaling.-Yang, Y., Qi, Q., Wang, Y., Shi, Y., Yang, W., Cen, Y., Zhu, E., Li, X., Chen, D., Wang, B. Cysteine-rich protein 61 regulates adipocyte differentiation from mesenchymal stem cells through mammalian target of rapamycin complex 1 and canonical Wnt signaling.

Association between circulating follistatin‐like‐1 and metabolic syndrome in middle‐aged and old population: A cross‐sectional study

“…These proteins are at the core of the FSTL‐1 protein interaction network. The interactive proteins listed in this study were mainly enriched in biological pathologic processes in response to adipocyte differentiation and inflammation of CYR61, 28 adipogenesis, inflammation, and angiogenesis for SPARC1 29‐31 ; hypertension and atherosclerotic lesions for LTBP1 32,33 ; lipolysis in skeletal muscle, inflammatory processes and IR for IL6 34 ; the differentiation of preadipocytes into white adipocytes for BMP2 35 ; hepatic lipid metabolism for BMP4 36 and non‐alcoholic fatty liver disease (NAFLD) for FSTL‐3 37 . In accord with the above analysis results, our Co‐IP experiment further confirmed the interaction between FSTL‐1 and BMP4 in vivo.…”

Simvastatin downregulates adipogenesis in 3T3-L1 preadipocytes and orbital fibroblasts from Graves’ ophthalmopathy patients

“…In the present study, both of these genes were rapidly expressed after stimulation of preadipocytes with CSE alone, and the magnitude of the expression was similar to the expression in response to the differentiation cocktail. CYR61 is a multifunctional gene with roles in adipogenesis, inflammation, cell proliferation, extracellular matrix production and fibrosis (25, 26, 27). Thus, there are several mechanisms by which CYR61 could contribute to the pathogenesis of GO.…”

Sparcl1 promotes nonalcoholic steatohepatitis progression in mice through upregulation of CCL2

“…In this study, using HFHC diet-induced mouse models that encompass 2 time periods, we compared the WAT transcriptome and identified 118 cytokines selectively dysregulated in the WAT of NASH mice. Some of these cytokines have been shown to regulate adipogenesis (such as Wnt10b and Angptl2), adipose inflammation (such as Gdf3 and Cyr61), and fat mass and energy expenditure (such as Fgf10 and Vegfb) in adipose tissues (66)(67)(68)(69)(70)(71). Whether they play a role in the development of NASH through direct or indirect mechanisms remains poorly understood.…”