title: KCa3.1: a new player in progressive kidney disease.
abstract: OBJECTIVE
  Hypertension and hyperglycaemia are major risk factors that result in chronic kidney disease (CKD). Achievement of blood pressure goals, optimal control of blood glucose levels and the use of agents to block the renin-angiotensin-aldosterone system slow the progression of CKD. However, not all patients are benefited by these interventions and novel strategies to arrest or reverse the pathological processes inherent in CKD are needed. The therapeutic potential of targeting KCa3.1 in CKD will be discussed in this review.
  
  
  RESULTS
  Blockade of KCa3.1 ameliorates activation of renal fibroblasts in diabetic mice by inhibiting the transforming growth factor-β1/small mothers against decapentaplegic pathway. A concomitant reduction in nuclear factor-κB activation in human proximal tubular cells under diabetic conditions has been observed. Advanced glycosylated endproducts induce both protein expression and current density of KCa3.1, which, in turn, mediates migration and proliferation of vascular smooth muscle cells via Ca²⁺-dependent signalling pathways.
  
  
  CONCLUSIONS
  Studies have clearly demonstrated a causal role of chronic hyperglycaemia and hypertension in the development of CKD. However, a large proportion of patients develop end-stage kidney disease despite strict glycaemic control and the attainment of recommended blood pressure goals. Therefore, it is essential to identify and validate novel targets to reduce the development and progression of CKD. Recent findings demonstrate that genetic deletion or pharmacologic inhibition of KCa3.1 significantly reduces the development of diabetic nephropathy in animal models. However, the consequences of blockade of KCa3.1 in preventing and treating established diabetic nephropathy in humans warrants further study.
authors.affiliation: Kolling Institute of Medical Research, Sydney Medical School, University of Sydney, Royal North Shore Hospital, St Leonards, New South Wales, Australia.
authors.forename: Chunling
authors.initials: C
authors.lastname: Huang
authors.forename: Carol A
authors.initials: CA
authors.lastname: Pollock
authors.forename: Xin-Ming
authors.initials: XM
authors.lastname: Chen
mesh_terms: D002465:Cell Movement; D049109:Cell Proliferation; D003928:Diabetic Nephropathies / Q000188:drug therapy* / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism; D017127:Glycation End Products, Advanced / Q000378:metabolism; D006801:Humans; D006973:Hypertension / Q000378:metabolism; D051660:Intermediate-Conductance Calcium-Activated Potassium Channels / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000502:physiology; D016328:NF-kappa B / Q000378:metabolism; D051436:Renal Insufficiency, Chronic / Q000188:drug therapy* / Q000378:metabolism / Q000517:prevention & control; D015398:Signal Transduction; D051785:Smad Proteins / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism
chemical_list: D017127:Glycation End Products, Advanced; D051660:Intermediate-Conductance Calcium-Activated Potassium Channels; C496923:KCNN4 protein, human; C496925:Kcnn4 protein, mouse; D016328:NF-kappa B; D051785:Smad Proteins; D016212:Transforming Growth Factor beta