title: The cytoskeleton as a novel target for treatment of renal fibrosis.
abstract: The incidence of chronic kidney disease (CKD) is increasing, with an estimated prevalence of 12% in the United States (Synder et al., 2009). While CKD may progress to end-stage renal disease (ESRD), which necessitates renal replacement therapy, i.e. dialysis or transplantation, most CKD patients never reach ESRD due to the increased risk of death from cardiovascular disease. It is well-established that regardless of the initiating insult - most often diabetes or hypertension - fibrosis is the common pathogenic pathway that leads to progressive injury and organ dysfunction (Eddy, 2014; Duffield, 2014). As such, there has been extensive research into the molecular and cellular mechanisms of renal fibrosis; however, translation to effective therapeutic strategies has been limited. While a role for the disruption of the cytoskeleton, most notably the actin network, has been established in acute kidney injury over the past two decades, a role in regulating renal fibrosis and CKD is only recently emerging. This review will focus on the role of the cytoskeleton in regulating pro-fibrotic pathways in the kidney, as well as data suggesting that these pathways represent novel therapeutic targets to manage fibrosis and ultimately CKD.
authors.affiliation: Department of Medical Pharmacology and Physiology, School of Medicine, University of Missouri, Columbia, MO 65212, USA. Electronic address: parrishar@health.missouri.edu.
authors.forename: Alan R
authors.initials: AR
authors.lastname: Parrish
mesh_terms: D000199:Actins / Q000378:metabolism*; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives; D003599:Cytoskeleton / Q000378:metabolism* / Q000473:pathology; D018450:Disease Progression; D004847:Epithelial Cells / Q000378:metabolism; D005355:Fibrosis; D006801:Humans; D007676:Kidney Failure, Chronic / Q000503:physiopathology; D050199:Podocytes / Q000378:metabolism; D051436:Renal Insufficiency, Chronic / Q000473:pathology / Q000503:physiopathology*; D054460:rho-Associated Kinases / Q000378:metabolism
chemical_list: C541116:ACTA2 protein, human; D000199:Actins; C018524:N,N-dimethylarginine; D001120:Arginine; D054460:rho-Associated Kinases
keywords: Actin; Chronic kidney disease; Cytoskeleton; Fibrosis; Microtubule