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Title: | ASK1: A new therapeutic target for kidney disease. | Authors: | Tesch G.H.;Ma F.Y.;Nikolic-Paterson D.J. | Institution: | (Tesch, Ma, Nikolic-Paterson) Department of Nephrology, Monash Medical Centre, Clayton, VIC, Australia (Tesch, Ma, Nikolic-Paterson) Monash University Department of Medicine, Monash Medical Centre, Clayton, VIC, Australia | Issue Date: | 7-Sep-2016 | Copyright year: | 2016 | Publisher: | American Physiological Society (E-mail: subscrip@the-aps.org) | Place of publication: | United States | Publication information: | American Journal of Physiology - Renal Physiology. 311 (2) (pp F373-F381), 2016. Date of Publication: 01 Aug 2016. | Journal: | American Journal of Physiology - Renal Physiology | Abstract: | Stress-induced activation of p38 MAPK and JNK signaling is a feature of both acute and chronic kidney disease and is associated with disease progression. Inhibitors of p38 MAPK or JNK activation provide protection against inflammation and fibrosis in animal models of kidney disease; however, clinical trials of p38 MAPK and JNK inhibitors in other diseases (rheumatoid arthritis and pulmonary fibrosis) have been disappointing. Apoptosis signal-regulating kinase 1 (ASK1) acts as an upstream regulator for the activation of p38 MAPK and JNK in kidney disease. Mice lacking the Ask1 gene are healthy with normal homeostatic functions and are protected from acute kidney injury induced by ischemia-reperfusion and from renal interstitial fibrosis induced by ureteric obstruction. Recent studies have shown that a selective ASK1 inhibitor substantially reduced renal p38 MAPK activation and halted the progression of nephropathy in diabetic mice, and this has led to a current clinical trial of an ASK1 inhibitor in patients with stage 3 or 4 diabetic kidney disease. This review explores the rationale for targeting ASK1 in kidney disease and the therapeutic potential of ASK1 inhibitors based on current experimental evidence.Copyright © 2016 the American Physiological Society. | DOI: | http://monash.idm.oclc.org/login?url=http://dx.doi.org/10.1152/ajprenal.00208.2016 | PubMed URL: | 27226108 [http://www.ncbi.nlm.nih.gov/pubmed/?term=27226108] | ISSN: | 0363-6127 | URI: | https://repository.monashhealth.org/monashhealthjspui/handle/1/39841 | Type: | Review | Subjects: | review acute kidney failure chronic kidney disease signal transduction ureter obstruction apoptosis signal regulating kinase 1/ec [Endogenous Compound] mitogen activated protein kinase p38/ec [Endogenous Compound] phosphotransferase inhibitor/dt [Drug Therapy] diabetic nephropathy/dt [Drug Therapy] unclassified drug ASK1 gene apoptosis signal regulating kinase 1 inhibitor/dt [Drug Therapy] stress activated protein kinase/ec [Endogenous Compound] disease course disease severity drug selectivity enzyme activation fibrosing alveolitis gene homeostasis human *kidney disease/dt [Drug Therapy] *kidney disease/et [Etiology] kidney disease/dt [Drug Therapy] nonhuman priority journal renal protection reperfusion injury human *kidney disease / *drug therapy / *etiology kidney disease / drug therapy nonhuman priority journal renal protection reperfusion injury Review chronic kidney disease ureter obstruction acute kidney failure signal transduction diabetic nephropathy / drug therapy disease course disease severity drug selectivity enzyme activation fibrosing alveolitis gene homeostasis |
Type of Clinical Study or Trial: | Review article (e.g. literature review, narrative review) |
Appears in Collections: | Articles |
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