Journal of RNA and Genomics

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Research Article - Journal of RNA and Genomics (2021) Volume 17, Issue 7

Potential roles of cytosolic and pro-urinary enzymes on the transient receptor potential cation channel subfamily V member 5 and nephrolithiasis

Nephrolithiasis is a common disease in clinical practice with large health care expenditures of all patients, about 70% forms Ca2+-containing stones. The most common form of nephrolithiasis is calcium oxalate. Calcium (Ca2+) is the important electrolyte in human body. Bone stores 99% of total body Ca2+ while the other 1% in blood circulation is filtered and reabsorbed by the kidneys. Proximal tubule passively reabsorbs Ca2+ while the late distal convoluted and connecting tubules (DCT2/CNT) reabsorb Ca2+ by means of active transport. The amount of active Ca2+ transport is minor, but crucial as the fine-tuner of final urinary Ca2+ concentration. The active Ca2+ reabsorption across the DCT2/CNT cells consists of 3 steps: apical uptake through the Transient Receptor Potential Cation Channel subfamily V member 5 (TRPV5) Ca2+ channel, cytosolic Ca2+ translocation by calbindin-D28K protein, and basolateral Ca2+ extrusion into the blood circulation by plasma membrane Ca2+ ATPase type 1b and Na+-Ca2+ exchanger type 1. TRPV5-mediated Ca2+ uptake is the rate-limiting step of active Ca2+ reabsorption. TRPV5 deficiency and gene polymorphism are associated with hypercalciuria and stone multiplicity of Ca2+ nephrolithiasis. This review is aimed to describe molecular mechanisms of TRPV5 regulation by cytosoilic enzymes (nucleoside diphosphate kinase B, immunophilins, protein kinase C substrate 80K-H, with-no-lysine kinases, serum and glucocorticoid inducible kinases, src kinases, dynamin GTPase, ubiquitin ligase and mediator of ERBB2-driven cell motility) and pro-urinary enzymes (tissue transglutaminase, klotho, plasmin, thrombin and tissue kallikrein) associated with nephrolithiasis. Relevant genomic action on TRPV5 mRNA expression and non-genomic actions on ion channel activities and membrane protein expression of the enzymes are elaborated. These enzymes might be important as pharmacological targets for renal Ca2+ stone management in clinical settings.

Author(s): Kukiat Tudpor

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