Sonic hedgehog signaling in kidney fibrosis: a master communicator
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- 作者：Dong Zhou ; Roderick J. Tan ; Youhua Liu
- 关键词：Sonic hedgehog ; Gli ; tubular cells ; fibroblast ; renal fibrosis
- 刊名：Science China Life Sciences
- 出版年：2016
- 出版时间：September 2016
- 年：2016
- 卷：59
- 期：9
- 页码：920-929
- 全文大小：1,635 KB
- 刊物主题：Life Sciences, general;
- 出版者：Springer Berlin Heidelberg
- ISSN：1869-1889
- 卷排序：59
文摘
The hedgehog signaling cascade is an evolutionarily conserved pathway that regulates multiple aspects of embryonic development and plays a decisive role in tissue homeostasis. As the best studied member of three hedgehog ligands, sonic hedgehog (Shh) is known to be associated with kidney development and tissue repair after various insults. Recent studies uncover an intrinsic link between dysregulated Shh signaling and renal fibrogenesis. In various types of chronic kidney disease (CKD), Shh is upregulated specifically in renal tubular epithelium but targets interstitial fibroblasts, thereby mediating a dynamic epithelial- mesenchymal communication (EMC). Tubule-derived Shh acts as a growth factor for interstitial fibroblasts and controls a hierarchy of fibrosis-related genes, which lead to the excessive deposition of extracellular matrix in renal interstitium. In this review, we recapitulate the principle of Shh signaling, its activation and regulation in a variety of kidney diseases. We also discuss the potential mechanisms by which Shh promotes renal fibrosis and assess the efficacy of blocking this signaling in preclinical settings. Continuing these lines of investigations will provide novel opportunities for designing effective therapies to improve CKD prognosis in patients.