Thiazide-induced hypocalciuria is accompanied by a decreased expression of Ca2+ transport proteins in kidney

Nijenhuis, Tom; Hoenderop, Joost G. J.; Loffing, Johannes; Kemp, Annemiete W.C.M. van der; Os, C.H. van; Bindels, René J. M.

doi:10.1046/j.1523-1755.2003.00128.x

Cited by 117 publications

(89 citation statements)

References 40 publications

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“…Furthermore, thiazides have been shown to increase bone mineral density and decrease fracture risk, spiking interest in the favorable long-term effects of these diuretics in counteracting osteoporosis (Reid et al 2000). The decreased Ca 2+ excretion during chronic thiazide administration has been explained by ECV contraction enhancing the paracellular Ca 2+ reabsorption in proximal tubules as well as a direct stimulation of active Ca 2+ reabsorption in the DCT (Costanzo et al 1978;Ellison 2000;Friedman 1998;Friedman and Bushinsky 1999;Loffing et al 2001;Nijenhuis et al 2003).…”

Section: Thiazide Diureticsmentioning

confidence: 99%

“…Some hypotheses concerning the mechanism responsible for this hypocalciuria also center on stimulation of active Ca 2+ transport (Ellison 2000). However, Nijenhuis et al showed that chronic hydrochlorothiazides (HCTZ) treatment consistently decreased the mRNA expression and protein abundance of the transporters responsible for active Ca 2+ reabsorption, including TRPV5, while prevention of ECV contraction during HCTZ treatment prohibited the development of hypocalciuria (Nijenhuis et al 2003). These results suggest that ECV contraction is the critical determinant of the thiazide-induced hypocalciuria, excluding a stimulatory role of TRPV5.…”

Section: Thiazide Diureticsmentioning

confidence: 99%

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The epithelial calcium channels TRPV5 and TRPV6: regulation and implications for disease

Abel

Hoenderop

Bindels

2005

Naunyn-Schmiedeberg's Arch Pharmacol

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The epithelial Ca 2+ channels TRPV5 and TRPV6 represent a new family of Ca 2+ channels that belongs to the superfamily of transient receptor potential channels. TRPV5 and TRPV6 constitute the apical Ca 2+ entry mechanism in active Ca 2+ transport in kidney and intestine. The central role of TRPV5 and TRPV6 in active Ca 2+ (re)absorption makes it a prime target for regulation to maintain Ca 2+ balance. This review covers the hormonal regulation, interaction with accessory proteins and (patho)physiological implications of these epithelial Ca 2+ channels.

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Section: Thiazide Diureticsmentioning

confidence: 99%

Section: Thiazide Diureticsmentioning

confidence: 99%

The epithelial calcium channels TRPV5 and TRPV6: regulation and implications for disease

Abel

Hoenderop

Bindels

2005

Naunyn-Schmiedeberg's Arch Pharmacol

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“…Indeed, although TRPV6 expression, regulation, and functions in intestine (13), kidney (23,24), and cancerous prostate (25,26) had been previously studied, the role of TRPV6 in the epidermis, where calcium plays a major role in cell physiopathology, was previously unknown.…”

Section: Trpv6 Channel Is a Likely Candidate For Mediating Camentioning

confidence: 99%

TRPV6 Is a Ca2+ Entry Channel Essential for Ca2+-induced Differentiation of Human Keratinocytes

Lehen’kyi

Beck

Polakowska

et al. 2007

Journal of Biological Chemistry

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Ca2؉ is an essential factor inducing keratinocyte differentiation due to the natural Ca 2؉ gradient in the skin. However, the membrane mechanisms that mediate calcium entry and trigger keratinocyte differentiation had not previously been elucidated.In this study we demonstrate that Ca 2؉ -induced differentiation up-regulates both mRNA and protein expression of a transient receptor potential highly Ca 2؉ -selective channel, TRPV6. The latter mediates Ca 2؉ uptake and accounts for the basal [Ca 2؉ ] i in human keratinocytes. Our results show that TRPV6 is a prerequisite for keratinocyte entry into differentiation, because the silencing of TRPV6 in human primary keratinocytes led to the development of impaired differentiated phenotype triggered by Ca 2؉ . The expression of such differentiation markers as involucrin, transglutaminase-1, and cytokeratin-10 was significantly inhibited by small interfering RNA-TRPV6 as compared with differentiated control cells. TRPV6 silencing affected cell morphology and the development of intercellular contacts, as well as the ability of cells to stratify. 1,25-Dihydroxyvitamin D3, a cofactor of differentiation, dose-dependently increased TRPV6 mRNA and protein expression in human keratinocytes. This TRPV6 up-regulation led to a significant increase in Ca 2؉ uptake in both undifferentiated and differentiated keratinocytes. We conclude that TRPV6 mediates, at least in part, the pro-differentiating effects of 1,25-dihydroxyvitamin D3 by increasing Ca 2؉ entry, thereby promoting differentiation. Taken together, these data suggest that the TRPV6 channel is a key element in Ca 2؉ /1,25-dihydroxyvitamin D3-induced differentiation of human keratinocytes.Human epidermis is the largest tissue of the body responsible for barrier function and is primarily composed of keratinocytes. Keratinocytes are arranged in highly organized, specialized layers according to their functions and the programmed life cycle. Proliferating keratinocytes comprise the stratum basale. As a result of proliferation, keratinocytes leave the stratum basale, moving toward the exterior with the onset of differentiation in the stratum spinosum. Differentiation is completed in the stratum granulosum, thereby constituting the enucleated stratum corneum, which plays the major role of permeability barrier.A number of auto-and paracrine factors drive keratinocyte differentiation. Calcium and 1,25-dihydroxyvitamin D3, an active metabolite of vitamin D, play important roles in this process (1). Cytosolic Ca 2ϩ signaling is well known to control a wide array of cell functions, ranging from shortterm responses such as contraction and secretion to longerterm regulation of cell growth and proliferation (2). The epidermis has a calcium gradient, with the lowest concentrations in the stratum basale and the highest in the stratum granulosum, where the proteins critical for barrier function are produced (3, 4). The keratinocyte response to extracellular calcium, i.e. "calcium switch" that induces differentiation, is not fully understood....

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“…Association of TRPC3 and TRPC6 with Apical Ca 2ϩ -signaling Proteins-Among the various TRP channels, TRPV5 and TRPV6 are apically localized in distal regions of renal tubules and gastric epithelium (30). These proteins are suggested to be involved in apical Ca 2ϩ reabsorption in distal tubules and collecting tubules of the kidney as well as from the gut lumen.…”

Section: Localization Of Trpc Proteins In Polarized Epithelialmentioning

confidence: 99%

Apical Localization of a Functional TRPC3/TRPC6-Ca2+-Signaling Complex in Polarized Epithelial Cells

Bandyopadhyay

Swaim

Liu

et al. 2005

Journal of Biological Chemistry

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Thiazide-induced hypocalciuria is accompanied by a decreased expression of Ca2+ transport proteins in kidney

Abstract: These data suggest that ECV contraction is a critical determinant of the thiazide-induced hypocalciuria, which is accompanied by a decreased expression of Ca2+ transport proteins.

Cited by 117 publications

References 40 publications

The epithelial calcium channels TRPV5 and TRPV6: regulation and implications for disease

The epithelial calcium channels TRPV5 and TRPV6: regulation and implications for disease

TRPV6 Is a Ca2+ Entry Channel Essential for Ca2+-induced Differentiation of Human Keratinocytes

Apical Localization of a Functional TRPC3/TRPC6-Ca2+-Signaling Complex in Polarized Epithelial Cells

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