TAZ-mediated enhancement of adipogenesis in goat adipose mesenchymal stem cells induced by TNF-α

Obesity is a clinical condition characterised by a chronic, low-grade inflammatory state. Adipose-derived mesenchymal stem cells (ADSCs) have a multidirectional differentiation potential to adipocytes. However, the relationship between adipogenesis and inflammation is not yet fully understood.TAZ (WW domain containing transcription regulator 1) can act as a molecular rheostat to fine-tune the osteoblast and adipocyte differentiation balance. In this study, we investigated the role of TAZ in the adipogenesis of Arbas cashmere goat ADSCs (gADSCs). We observed elevated TAZ expression levels during the adipogenesis of gADSCs. Overexpression and knockdown of TAZ were performed in stably transfected gADSCs cell lines, and RNA-seq analysis revealed that TAZ was associated with adipogenesis. TAZ overexpression promoted adipose differentiation of gADSCs, while TAZ knockdown had the opposite effect. In addition, TAZ overexpression and knockdown altered the expression of YAP1 (Yes1 associated transcriptional regulator) and TAZ in the nucleus. TAZ regulated the mRNA expression level and secretion level of tumor necrosis factor (TNF)-α, promoting adipose differentiation of gADSCs. Notably, TNF-α counteracted the inhibitory effect of sh-TAZ on the adipose differentiation of gADSCs. Collectively, these findings suggest that TAZ regulates adipogenesis in gADSCs by modulating TNF-α, which is of particular significance in several metabolic disorders where the amount or function of adipose tissue is altered. To investigate the effect of TAZ on adipogenesis of gADSCs, we constructed gADSCs cell lines OE-TAZ. RNA-seq was performed with OE-TAZ and Control cells. Based on the RNA-seq data, an expression profile was generated.

肥胖是一种以慢性低度炎症状态为特征的临床病症。脂肪间充质干细胞（Adipose-derived mesenchymal stem cells, ADSCs）具有向脂肪细胞分化的多向分化潜能。然而，成脂分化与炎症之间的关系尚未完全阐明。TAZ（WW domain containing transcription regulator 1）可作为分子变阻器，微调成骨细胞与脂肪细胞的分化平衡。本研究探讨了TAZ在阿尔巴斯绒山羊脂肪间充质干细胞（Arbas cashmere goat ADSCs, gADSCs）成脂分化中的作用。我们观察到，在gADSCs的成脂分化过程中TAZ的表达水平升高。本研究通过构建稳定转染的gADSCs细胞系，分别实施TAZ过表达与TAZ敲低实验；RNA测序（RNA-seq）分析显示，TAZ与成脂分化密切相关。TAZ过表达可促进gADSCs的脂肪分化，而TAZ敲低则产生相反效应。此外，TAZ过表达与敲低均可改变细胞核内YAP1（Yes1 associated transcriptional regulator）与TAZ的表达水平。TAZ可调节肿瘤坏死因子α（tumor necrosis factor, TNF-α）的mRNA表达水平与分泌水平，进而促进gADSCs的脂肪分化。值得注意的是，TNF-α可抵消sh-TAZ对gADSCs脂肪分化的抑制作用。综上，本研究结果表明，TAZ通过调控TNF-α参与gADSCs的成脂分化过程，这在脂肪组织数量或功能异常的多种代谢紊乱中具有重要意义。为探究TAZ对gADSCs成脂分化的影响，我们构建了OE-TAZ型gADSCs细胞系，并对OE-TAZ组与对照组细胞进行RNA测序。基于该RNA测序数据，我们生成了基因表达谱。