Signalling pathways involved in hypoxia‐induced renal fibrosis

Renal fibrosis is the common pathological hallmark of progressive chronic kidney disease (CKD) with diverse aetiologies. Recent researches have highlighted the critical role of hypoxia during the development of renal fibrosis as a final common pathway in end-stage kidney disease (ESKD), which joints the scientist's attention recently to exploit the molecular mechanism underlying hypoxia-induced renal fibrogenesis. The scaring formation is a multilayered cellular response and involves the regulation of multiple hypoxia-inducible signalling pathways and complex interactive networks. Therefore, this review will focus on the signalling pathways involved in hypoxia-induced pathogenesis of interstitial fibrosis, including pathways mediated by HIF, TGF-β, Notch, PKC/ERK, PI3K/Akt, NF-κB, Ang II/ROS and microRNAs. Roles of molecules such as IL-6, IL-18, KIM-1 and ADO are also reviewed. A comprehensive understanding of the roles that these hypoxia-responsive signalling pathways and molecules play in the context of renal fibrosis will provide a foundation towards revealing the underlying mechanisms of progression of CKD and identifying novel therapeutic targets. In the future, promising new effective therapy against hypoxic effects may be successfully translated into the clinic to alleviate renal fibrosis and inhibit the progression of CKD.