RWTH University Hospital Aachen, Institute of Clinical Chemistry and Pathobiochemistry, Aachen, Germany.
Front Biosci (Landmark Ed). 2013 Jun 1;18(4):1407-34. doi: 10.2741/4189.
Chronic organ injuries are accompanied by a dysregulated scarring process called "Fibrosis" that is characterized by hyperactivity of TGF-beta resulting in an imbalance of extracellular matrix homeostasis and accumulation of fibrosis-associated proteins. These changes are due to a specialized matrix-expressing cell type, i.e. the myofibroblast, which is derived from independent cellular sources. Beside resident quiescent fibroblasts that become activated, circulating bone-marrow-derived fibrocytes are attracted by the injured organ. Additionally, epithelial cells transit into mesenchymal cells in a process termed epithelial-to-mesenchymal transition. Furthermore, mesothelial cells leave their peripheral location and acquire a fibrogenic phenotype via mesothelial-to-mesenchymal transition. Numerous independent studies have consistently demonstrated that BMP-7 interferes with TGF-betasignaling and a diverse set of matricellular proteins (e.g. CCN proteins), Endoglin, Betaglycan, BAMBI and the members of the repulsive guidance molecule family that modulate cellular proliferation, migration, adhesion and extracellular matrix production. This protein network might therefore depict novel targets for treatment of fibrotic lesions. We here summarize recent knowledge of BMP-7 function and discuss attempts to use this cytokine as a drug to reverse TGF-beta-induced fibrogenesis.
慢性器官损伤伴随着失调的瘢痕形成过程，称为“纤维化”，其特征是 TGF-β的过度活跃，导致细胞外基质稳态失衡和纤维化相关蛋白的积累。这些变化是由于一种特殊的基质表达细胞类型，即肌成纤维细胞，它来源于独立的细胞来源。除了静息的成纤维细胞被激活外，循环骨髓源性成纤维细胞也被受损器官吸引。此外，上皮细胞通过上皮-间充质转化（EMT）转化为间充质细胞。此外，间皮细胞通过间皮-间充质转化（EndMT）离开其外周位置并获得成纤维表型。许多独立的研究一致表明，BMP-7 干扰 TGF-β信号和一组多样化的细胞外基质蛋白（如 CCN 蛋白）、Endoglin、Betaglycan、BAMBI 和排斥性导向分子家族成员，调节细胞增殖、迁移、黏附和细胞外基质的产生。因此，这个蛋白质网络可能描绘了治疗纤维化病变的新靶点。我们在这里总结了 BMP-7 功能的最新知识，并讨论了使用这种细胞因子作为药物来逆转 TGF-β诱导的纤维化的尝试。
