Concerted action of associated proteins in the regulation of TRPV5 and TRPV6

Schoeber, Joost P. H.; Hoenderop, Joost G. J.; Bindels, René J. M.

doi:10.1042/bst0350115

Cited by 44 publications

(37 citation statements)

References 40 publications

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“…Shuttling of TRPV5 to and from a subapical pool is a key component of this regulation, and high Ca 2ϩ influx may be obtained by prolonging the channel's durability at the cell surface before inactivation or internalization. Klotho, through its glucuronidase activity, modulates N-glycosylation of TRPV5 at Asn358 by removal of the capping sialic acid, which enables physical interaction of galectin 1 with TRPV5 on the cell surface and promotes its apical retention (89 In our laboratory's recent study (101), we described that renal Klotho is significantly downregulated in experimental colitis. This was consistently observed in three distinct models of murine IBD: TNBS colitis, SPF-associated germ-free IL-10 Ϫ/Ϫ mice, and CD4 ϩ CD45RB Hi T-cell transfer colitis.…”

Section: Role Of Klotho In Epithelial Ca 2ϩ and P I Transportmentioning

confidence: 94%

Advances in the understanding of mineral and bone metabolism in inflammatory bowel diseases

Ghishan

Kiela

2011

American Journal of Physiology-Gastrointestinal and Liver Physi

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Ghishan FK, Kiela PR. Advances in the understanding of mineral and bone metabolism in inflammatory bowel diseases. Am J Physiol Gastrointest Liver Physiol 300: G191-G201, 2011. First published November 18, 2010 doi:10.1152/ajpgi.00496.2010.-Chronic inflammatory disorders such as inflammatory bowel diseases (IBDs) affect bone metabolism and are frequently associated with the presence of osteopenia, osteoporosis, and increased risk of fractures. Although several mechanisms may contribute to skeletal abnormalities in IBD patients, inflammation and inflammatory mediators such as TNF, IL-1␤, and IL-6 may be the most critical. It is not clear whether the changes in bone metabolism leading to decreased mineral density are the result of decreased bone formation, increased bone resorption, or both, with varying results reported in experimental models of IBD and in pediatric and adult IBD patients. New data, including our own, challenge the conventional views, and contributes to the unraveling of an increasingly complex network of interactions leading to the inflammationassociated bone loss. Since nutritional interventions (dietary calcium and vitamin D supplementation) are of limited efficacy in IBD patients, understanding the pathophysiology of osteopenia and osteoporosis in Crohn's disease and ulcerative colitis is critical for the correct choice of available treatments or the development of new targeted therapies. In this review, we discuss current concepts explaining the effects of inflammation, inflammatory mediators and their signaling effectors on calcium and phosphate homeostasis, osteoblast and osteoclast function, and the potential limitations of vitamin D used as an immunomodulator and anabolic hormone in IBD.bone mineral density; Crohn's disease; osteopenia; osteoporosis; ulcerative colitis INFLAMMATORY BOWEL DISEASES (IBDs) represent a group of chronic inflammatory disorders of the intestinal tract that to this date remains idiopathic. More recent basic and clinical research indicates that the chronic inflammatory reaction of the intestinal mucosa is directed against the gut microbiota in individuals with genetic and/or environmental susceptibilities. Disease onset occurs typically during young adulthood (25-35 yr), although ϳ20 -25% of cases are diagnosed during childhood (93). On a clinical basis, two major subtypes of IBD are defined as Crohn's disease (CD), which potentially affects any part of the gastrointestinal tract from the mouth to the anus, and ulcerative colitis (UC), an inflammatory condition limited to the colonic mucosa. However, IBD does not affect just a single organ and should be considered a systemic disease with several extraintestinal manifestations, which occur in a large proportion of IBD patients (60). Osteopenia and osteoporosis are two of the more common extraintestinal symptoms with a general consensus that IBD patients are at a significantly higher risk of developing metabolic bone disease and low bone mineral density (BMD) than the healthy subjects. The relative risk of fractur...

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Section: Role Of Klotho In Epithelial Ca 2ϩ and P I Transportmentioning

confidence: 94%

Advances in the understanding of mineral and bone metabolism in inflammatory bowel diseases

Ghishan

Kiela

2011

American Journal of Physiology-Gastrointestinal and Liver Physi

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“…TRPV6, mainly expressed by intestinal epithelial cells and the colon cell line, Caco2, is highly selective for Ca 2+ transport and is therefore important for Ca 2+ absorption in the gut [108,109,110]. This channel is regulated by dietary factors and calciotropic hormones [108,111,112,113,114]. Disturbed Ca 2+ homeostasis is associated with a CD-like pathology and may lead to osteoporosis [115].…”

Section: Trp Channels In the Inflamed Gutmentioning

confidence: 99%

Transient Receptor Potential Channels in Intestinal Inflammation: What Is the Impact of Cigarette Smoking?

Allais

Smet²,

Verschuere³

et al. 2016

Pathobiology

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Inflammatory bowel disease (IBD) is characterized by severe gastrointestinal inflammation and results from a complex interplay between genetic and environmental factors. IBD includes two prominent subtypes: Crohn's disease (CD) and ulcerative colitis (UC). One of the main risk factors for the development of CD is cigarette smoking, while UC is rather a disease of ex-smokers. To date, many of the mechanisms underlying the immune imbalance in IBD and the involvement of cigarette smoke (CS) are incompletely understood. Transient receptor potential (TRP) proteins are non-selective cation channels that, upon activation, lead to plasma membrane depolarization and, in general, to Ca²⁺ influx. TRP channels of the ankyrin and vanilloid family, expressed by sensory neurons in the central and enteric nervous systems, have been extensively studied in the context of intestinal inflammation. Moreover, recent advances made on the role of non-neuronal expressed TRP channels shed light on the involvement of epithelial cells in inflammatory processes. This review focuses on how CS may impact TRP channel function in intestinal inflammation. Firstly, we discuss the current knowledge on neuronal TRP channels, known to be linked to IBD, in health, immune homeostasis and intestinal inflammation. Subsequently, we address how TRP channels are activated by CS and its components in other organ systems and also hypothesize on the potential implications for CS-mediated TRP channel activation in gut inflammation.

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“…Klotho is a ␤-glucuronidase that hydrolyzes extracellular sugar residues on TRPV5, entrapping the channel in the plasma membrane. Klotho effects are primarily restricted to the epithelial Ca 2ϩ channels TRPV5 and TRPV6 (Chang et al, 2005;Schoeber et al, 2007;Lu et al, 2008).…”

Section: Trpv5 and Trpv6 Agonistsmentioning

confidence: 99%