Hypercalciuria switches Ca²⁺ signaling in proximal tubular cells, induces oxidative damage to promote calcium nephrolithiasis.

ABSTRACT: Proximal tubule (PT) transports most of the renal Ca²⁺, which was usually described as paracellular (passive). We found a regulated Ca²⁺ entry pathway in PT cells via the apical transient receptor potential canonical 3 (TRPC3) channel, which initiates transcellular Ca²⁺ transport. Although TRPC3 knockout (-/-) mice were mildly hypercalciuric and displayed luminal calcium phosphate (CaP) crystals at Loop of Henle (LOH), no CaP + calcium oxalate (CaOx) mixed urine crystals were spotted, which are mostly found in calcium nephrolithiasis (CaNL). Thus, we used oral calcium gluconate (CaG; 2%) to raise the PT luminal [Ca²⁺]_o further in TRPC3 ^-/- mice for developing such mixed stones to understand the mechanistic role

SUBMITTER: Shin S 

PROVIDER: S-EPMC8843860 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature