Latent Transforming Growth Factor β Binding Protein 3 Controls Adipogenesis

Transforming growth factor-beta (TGFβ) is released from cells as part of a trimeric latent complex consisting of TGFβ, the TGFβ propeptides, and either a latent TGFβ binding protein (LTBP) or glycoprotein-A repetitions predominant (GARP) protein. LTBP1 and 3 modulate latent TGFβ function with respect to secretion, matrix localization, and activation and, therefore, are vital for the proper function of the cytokine in a number of tissues. TGFβ modulates stem cell differentiation into adipocytes (adipogenesis), but the potential role of LTBPs in this process has not been studied. We observed that 72 h post adipogenesis initiation Ltbp1, 2, and 4 expression levels decrease by 74-84%, whereas Ltbp3 expression levels remain constant during adipogenesis. We found that LTBP3 silencing in C3H/10T1/2 cells reduced adipogenesis, as measured by the percentage of cells with lipid vesicles and the expression of the transcription factor peroxisome proliferator-activated receptor gamma (PPARγ). Lentiv...转化生长因子-β（Transforming growth factor-beta, TGFβ）以三聚体潜伏复合物的形式从细胞中释放，该复合物由TGFβ、TGFβ前肽，以及潜伏TGFβ结合蛋白（latent TGFβ binding protein, LTBP）或糖蛋白A重复序列主要蛋白（glycoprotein-A repetitions predominant, GARP）组成。LTBP1与LTBP3可在分泌、基质定位及活化过程中调控潜伏TGFβ的功能，因此对于多种组织中该细胞因子的正常功能发挥至关重要。TGFβ能够调控干细胞向脂肪细胞的分化（脂肪生成），但LTBPs在此过程中的潜在作用尚未得到研究。我们观察到，在脂肪生成启动72小时后，Ltbp1、Ltbp2及Ltbp4的表达水平下调74%~84%，而Ltbp3的表达水平在整个脂肪生成过程中保持稳定。我们发现，在C3H/10T1/2细胞中沉默LTBP3会削弱脂肪生成能力，该效应可通过脂囊泡阳性细胞占比以及转录因子过氧化物酶体增殖物激活受体γ（peroxisome proliferator-activated receptor gamma, PPARγ）的表达水平得以验证。慢病毒（Lentiv...）