Hope Heart Program, Benaroya Research Institute at Virginia Mason, 1201 9th Ave, Seattle, WA 98101 USA.
J Cell Commun Signal. 2009 Dec;3(3-4):247-54. doi: 10.1007/s12079-009-0064-4. Epub 2009 Oct 2.
Adipogenesis, a key step in the pathogenesis of obesity, involves extensive ECM remodeling, changes in cell-ECM interactions, and cytoskeletal rearrangement. Matricellular proteins regulate cell-cell and cell-ECM interactions. Evidence in vivo and in vitro indicates that the prototypic matricellular protein, SPARC, inhibits adipogenesis and promotes osteoblastogenesis. Herein we discuss mechanisms underlying the inhibitory effect of SPARC on adipogenesis. SPARC enhances the Wnt/beta-catenin signaling pathway and regulates the expression and posttranslational modification of collagen. SPARC might drive preadipocytes away from the status of growth arrest and therefore prevent terminal differentiation. SPARC could also decrease WAT deposition through its negative effects on angiogenesis. Therefore, several stages of white adipose tissue accumulation are sensitive to the inhibitory effects of SPARC.
脂肪生成是肥胖发病机制中的一个关键步骤，涉及广泛的细胞外基质重塑、细胞-细胞外基质相互作用的变化和细胞骨架重排。基质细胞蛋白调节细胞-细胞和细胞-细胞外基质的相互作用。体内和体外的证据表明，典型的基质细胞蛋白，SPARC，抑制脂肪生成并促进成骨细胞生成。本文讨论了 SPARC 抑制脂肪生成的作用机制。SPARC 增强 Wnt/β-连环蛋白信号通路，并调节胶原蛋白的表达和翻译后修饰。SPARC 可能使前脂肪细胞脱离生长停滞状态，从而阻止终末分化。SPARC 还可以通过对血管生成的负性影响来减少 WAT 的沉积。因此，白色脂肪组织积累的几个阶段对 SPARC 的抑制作用敏感。
