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001-es BibID:BIBFORM070903
Első szerző:Ambrus Lídia (élettanász)
Cím:Human podocytes express functional thermosensitive transient receptor potential vanilloid (TRPV) channels / Lídia Ambrus, Balázs Kelemen, Tamás Szabó, Tamás Bíró, Balázs István Tóth
Dátum:2017
ISSN:0007-1188
Megjegyzések:BACKGROUND AND PURPOSEHeat sensitive transient receptor potential vanilloid (TRPV) channels are expressed in various epithelial tissues regulating, among else, barrier functions. Their expression is well established in the distal nephron; however, we have no data about their presence in podocytes. Since podocytes are indispensable in the formation of the glomerular filtration barrier, we investigated the presence and function of Ca2+-permeable TRPV1-4 channels in human podocyte cultures.EXPERIMENTAL APPROACHThe expression of TRPV1-4 was investigated at protein (immunocytochemistry, western blot) and mRNA (Q-PCR) level in a conditionally immortalized human podocyte cell line. The channel functionality was assessed by measuring intracellular Ca2+ concentration using fluo-4 Ca2+-indicator dye and patch clamp electrophysiology upon applying various activators and inhibitors.KEY RESULTSThermosensitive TRP channels were expressed in podocytes. The TRPV1 specific agonists capsaicin and resiniferatoxin did not induce any alteration in the intracellular Ca2+ concentration. Cannabidiol, an activator of TRPV2 and TRPV4 induced moderate Ca2+-influxes which were inhibited by both tranilast and HC067047, blockers of TRPV2 and TRPV4, respectively. The TRPV4-specific agonists GSK1016790A and 4?-Phorbol 12,13-didecanoate resulted robust Ca2+-signals which were abolished in the presence of HC067047. Non-specific agonists of TRPV3 induced marked Ca2+ transients. However, TRPV3 blockers, ruthenium red and isopentenyl diphosphate only partially inhibited the responses and TRPV3 silencing was ineffective suggesting remarkable off-target effects of the compounds.CONCLUSION AND IMPLICATIONSOur results indicate the functional presence of TRPV4 and other thermosensitive TRPV channels in human podocytes and raise the possibility of their involvement in the regulation of glomerular filtration barrier.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
folyóiratcikk
Megjelenés:British journal of pharmacology. - 174 : 23 (2017), p. 4493-4507. -
További szerzők:Kelemen Balázs (1992-) (biológus) Szabó Tamás (1968-) (gyermekgyógyász) Bíró Tamás (1968-) (élettanász) Tóth István Balázs (1978-) (élettanász)
Pályázati támogatás:76065
OTKA
NKFI K_16 120187
Egyéb
NKFI K_16 120552
Egyéb
TÁMOP-4.2.2.A-11/1/KONV-2012-0045
TÁMOP
LP003-2011/2015
Egyéb
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