Male hypercalciuric stone formers with low renal calcium reabsorption

Walker, Valerie; Cook, Paul; Griffin, D.

doi:10.1136/jclinpath-2013-201879

Cited by 5 publications

(2 citation statements)

References 23 publications

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“…Traditionally, the biochemical basis for stone formation is supersaturation of urine with relation to the stone minerals, involving increased supersaturation of calcium and oxalate [ 2 ]. Recent data reported that as many as 30%–50% of male stone formers investigated in stone clinics have hypercalciuria, which in most cases is idiopathic [ 3 ]. To our knowledge, idiopathic hypercalciuria (IH) is the finality of the interaction between genetic background and environment.…”

Section: Introductionmentioning

confidence: 99%

The Wnt11 Signaling Pathway in Potential Cellular EMT and Osteochondral Differentiation Progression in Nephrolithiasis Formation

et al. 2015

IJMS

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The molecular events leading to nephrolithiasis are extremely complex. Previous studies demonstrated that calcium and transforming growth factor-β1 (TGF-β1) may participate in the pathogenesis of stone formation, but the explicit mechanism has not been defined. Using a self-created genetic hypercalciuric stone-forming (GHS) rat model, we observed that the increased level of serous/uric TGF-β1 and elevated intracellular calcium in primary renal tubular epithelial cells (PRECs) was associated with nephrolithiasis progression in vivo. In the setting of high calcium plus high TGF-β1 in vitro, PRECs showed great potential epithelial to mesenchymal transition (EMT) progression and osteochondral differentiation properties, representing the multifarious increased mesenchymal and osteochondral phenotypes (Zeb1, Snail1, Col2A1, OPN, Sox9, Runx2) and decreased epithelial phenotypes (E-cadherin, CK19) bythe detection of mRNAs and corresponding proteins. Moreover, TGF-β-dependent Wnt11 knockdown and L-type Ca2+ channel blocker could greatly reverse EMT progression and osteochondral differentiation in PRECs. TGF-β1 alone could effectively promote EMT, but it had no effect on osteochondral differentiation in NRK cells (Rat kidney epithelial cell line). Stimulation with Ca2+ alone did not accelerate differentiation of NRK. Co-incubation of extracellular Ca2+ and TGF-β1 synergistically promotes EMT and osteochondral differentiation in NRK control cells. Our data supplied a novel view that the pathogenesis of calcium stone development may be associated with synergic effects of TGF-β1 and Ca2+, which promote EMT and osteochondral differentiation via Wnt11 and the L-type calcium channel.

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Section: Introductionmentioning

confidence: 99%

The Wnt11 Signaling Pathway in Potential Cellular EMT and Osteochondral Differentiation Progression in Nephrolithiasis Formation

et al. 2015

IJMS

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“…One of the initial steps for the formation of calcium oxalate stones is urine becoming supersaturated . Idiopathic hypercalciurie , low water intake, high protein or vitamin c intake and food rich in oxalate may lead to this . Another cause for urolithiasis in men is hyperuricosuria, which leads to acid urine and favours the formation of uric acid stones such as calcium oxalate stones .…”

Section: Resultsmentioning

confidence: 99%