Signalling pathways involved in hypoxia‐induced renal fibrosis

Abstract

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.

The PKCβ-p66shc-NADPH oxidase pathway plays a crucial role in diabetic nephropathy

“…A large number of studies have demonstrated that oxidative stress played an important role in the development of DN . ROS, produced by oxidative stress, caused renal impairment by activating related transcriptional proteins and cytokines . This study aimed to explore oxidative stress pathways associated with early DN.…”

“…[13,14] ROS, produced by oxidative stress, caused renal impairment by activating related transcriptional proteins and cytokines. [15,16] This study aimed to explore oxidative stress pathways associated with early DN. Injection of STZ was applied to induce early DN model.…”

Lysophosphatidic Acid Induces Ligamentum Flavum Hypertrophy Through the LPAR1/Akt Pathway

“…Constitutive activation of the Akt pathway has been found in a variety of fibrotic diseases, including cardiac [29, 30], renal [31, 32] and pulmonary fibrosis [33, 34]. Here, we demonstrated that LPA-LPAR1 induced Gai/o-Gγ-Gβ and PI3K in LF cells and activated Akt phosphorylation at Ser473 via TORC2 (Fig.…”

The relationship between haemoglobin level and type 1 diabetic nephropathy in Han patients in Anhui, China

“…The persistent low Hb level associated with impaired oxygen delivery is the main cause of chronic hypoxia, which has been considered to be closely associated with CKD. [15][16][17][18][19][20][21][22][23][24][25] Hypoxia inducible factor 1 (HIF-1) plays an important role in the transcriptional responses to hypoxia which may be closely associated with chronic renal injuries, including DN. [26][27][28] Previous studies show that in a streptozotocin-induced diabetes mouse model, HIF-1 has an important role in the early response to prevent diabetes-induced tissue damage and renal injury is accelerated by hypoxia-inducible factor 1α deficiency.…”