Origin and function of myofibroblasts in kidney fibrosis

 Raghu Kalluri, Valerie S LeBleu, and Hikaru Sugimoto et al. Nat Med. (2013) 19, 1047-53

Speaker: Jia-Ying Hung (洪家瑩)                                Time: 14:10~15:00, Mar. 12, 2014

Commentator: Dr. Ai-Li Shiau (蕭璦莉博士)               Place: Room 601

Abstract

Myofibroblasts play an important role in organ fibrosis. In wound healing, myofibroblasts will disappear when repair is accomplished. But in organ fibrosis, myofibroblasts do not disappear and extracellular matrix (ECM) keep accumulating. As a result, accumulated ECM replace the functional parenchyma of the organ and contribute to failure. Unfortunately, there is still no specific treatment to control fibrosis and preserve organ function except for targeting of immune mediators. Recently, myofibroblasts targeting therapy was proposed. But it remains a challenge because of incomplete knowledge of their origins and functional contribution. There were many speculations of the sources of myofiboblasts and can be classified into: vascular pericytes (1), epithelial-to-mesenchymal transition (EMT) (2), endothelial-to-mesenchymal transition (EndMT) (3) and bone marrow (4). To determine the origins and functional role of myofibroblasts in kidney fibrosis, the authors generated several genetic mouse models to track, fate map and eliminate myofibroblasts. The authors dem­onstrated that myofibroblasts are functional contributors of collagen production and kidney fibrosis. The results revealed that accumulation of myofibroblasts occurs predominantly from resident tissue fibroblasts (~50%), and (35%) bone marrow–derived cells. And bone marrow-derived cells did not proliferate in the kidney. The authors also showed that bone marrow–derived cells can differentiate into myofibroblasts through TGF-β1 signaling, and the recruitment of bone mar­row cells is dependent on the expression of type II TGF-β receptor (Tgfbr2). These findings suggested new therapeutic targets for kidney fibrosis, given great potential of applications in organ fibrosis prevention.

References

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