Cathepsin S promotes human preadipocyte differentiation:: Possible involvement of fibronectin degradation
Cathepsin S promotes human preadipocyte differentiation:: Possible involvement of fibronectin degradation
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DOI：
10.1210/en.2006-0386
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发表时间：
2006-10-01
期刊：
影响因子：
4.8
通讯作者：
Lacasa, Daniele
中科院分区：
文献类型：
--
作者：
Taleb, Soraya;Cancello, Raffaella;Lacasa, Daniele
我们之前表明，半胱氨酸蛋白酶组织蛋白酶 S (CTSS) 可以降解细胞外基质 (ECM) 的多种成分，它是由人类脂肪细胞产生的，并且在肥胖时会增加。由于 ECM 重塑是与脂肪生成相关的关键过程，这促使我们评估 CTSS 促进前脂肪细胞分化的潜在作用。原代人前脂肪细胞的动力学研究表明，分化末期 CTSS 基因表达和分泌略有增加。 CTSS 活性在前脂肪细胞培养基中最高，但此后下降，与分化过程中 CTSS 内源抑制剂胱抑素 C 释放的增加相符。通过在分化过程中添加的外源特异性抑制剂来抑制 CTSS 活性，导致分化细胞中的脂质含量和脂肪细胞标记物的表达减少 2 倍。相反，用人重组 CTSS 处理前脂肪细胞会增加脂肪生成。此外，在前脂肪细胞培养基中补充 CTSS 显着减少了纤连蛋白网络，纤连蛋白网络是前脂肪细胞 ECM 的关键成分，其减少是脂肪生成所必需的。通过对肥胖受试者脂肪组织的连续切片进行免疫组织化学分析，我们发现 CTSS 染色阳性的脂肪细胞主要位于含有纤连蛋白的纤维化区域附近。在此，我们提出 CTSS 可能至少部分通过在分化的早期步骤中降解纤连蛋白来促进人类脂肪生成。总而言之，这些结果表明前脂肪细胞局部释放的 CTSS 促进脂肪生成，表明这种蛋白酶可能对肥胖症中的脂肪量膨胀有贡献。
We previously showed that the cysteine protease cathepsin S (CTSS), known to degrade several components of the extracellular matrix (ECM), is produced by human adipose cells and increased in obesity. Because ECM remodeling is a key process associated with adipogenesis, this prompted us to assess the potential role of CTSS to promote preadipocyte differentiation. Kinetic studies in primary human preadipocytes revealed a modest increase in CTSS gene expression and secretion at the end of differentiation. CTSS activity was maximal in preadipocyte culture medium but decreased thereafter, fitting with increased release of the CTSS endogenous inhibitor, cystatin C, during differentiation. Inhibition of CTSS activity by an exogenous-specific inhibitor added along the differentiation, resulted in a 2-fold reduction of lipid content and expression of adipocyte markers in differentiated cells. Conversely, the treatment of preadipocytes with human recombinant CTSS increased adipogenesis. Moreover, CTSS supplementation in preadipocyte media markedly reduced the fibronectin network, a key preadipocyte-ECM component, the decrease of which is required for adipogenesis. Using immunohistochemistry on serial sections of adipose tissue of obese subjects, we showed that adipose cells staining positive for CTSS are mainly located in the vicinity of fibrosis regions containing fibronectin. Herein we propose that CTSS may promote human adipogenesis, at least in part, by degrading fibronectin in the early steps of differentiation. Taken together, these results indicate that CTSS released locally by preadipocytes promotes adipogenesis, suggesting a possible contribution of this protease to fat mass expansion in obesity.