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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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DOI
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2.

001-es BibID:BIBFORM060756
Első szerző:Ambrus Lídia (élettanász)
Cím:Inhibition of TRPC6 by protein kinase C isoforms in cultured human podocytes / Lídia Ambrus, Attila Oláh, Tamás Oláh, György Balla, Moin A. Saleem, Petronella Orosz, Judit Zsuga, Klára Bíró, László Csernoch, Tamás Bíró, Tamás Szabó
Dátum:2015
ISSN:1582-1838
Megjegyzések:Transient receptor potential canonical-6 (TRPC6) ion channels, expressed at high levels in podocytes of the filtration barrier, are recently implicated in the pathogenesis of various forms of proteinuric kidney diseases. Indeed, inherited or acquired up-regulation of TRPC6 activities are suggested to play a role in podocytopathies. Yet, we possess limited information about the regulation of TRPC6 in human podocytes. Therefore, in this study, we aimed at defining how the protein kinase C (PKC) system, one of the key intracellular signalling pathways, regulates TRPC6 function and expression. On human differentiated podocytes, we identified the molecular expressions of both TRPC6 and several PKC isoforms. We also showed that TRPC6 channels are functional since the TRPC6 activator 1-oleoyl-2-acetyl-sn-glycerol (OAG) induced Ca2+-influx to the cells. By assessing the regulatory roles of the PKCs, we found that inhibitors of the endogenous activities of classical and novel PKC isoforms markedly augmented TRPC6 activities. In contrast, activation of the PKC system by phorbol 12-myristate 13-acetate (PMA) exerted inhibitory actions on TRPC6 and suppressed its expression. Importantly, PMA treatment markedly down-regulated the expression levels of PKCa, PKCb, and PKCg reflecting their activation. Taken together, these results indicate that the PKC system exhibits a 'tonic' inhibition on TRPC6 activity in human podocytes suggesting that pathological conditions altering the expression and/or activation patterns of podocyte-expressed PKCs may influence TRPC6 activity and hence podocyte functions. Therefore, it is proposed that targeted manipulation of certain PKC isoforms might be beneficial in certain proteinuric kidney diseases with altered TRPC6 functions.
Tárgyszavak:Orvostudományok Klinikai orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
human podocytes
transient receptor potential canonical-6
protein kinase C isoforms
proteinuria
Megjelenés:Journal Of Cellular And Molecular Medicine. - 19 : 12 (2015), p. 2771-2779. -
További szerzők:Oláh Attila (1984-) (élettanász) Oláh Tamás (1983-) (élettanász) Balla György (1953-) (csecsemő és gyermekgyógyász, neonatológus) Saleem, Moin A. Orosz Petronella (1986-) (klinikai orvos) Zsuga Judit (1973-) (neurológus, pszichoterapeuta, egészségügyi szakmanager) Bíró Klára (1970-) (egészségügyi menedzsment) Csernoch László (1961-) (élettanász) Bíró Tamás (1968-) (élettanász) Szabó Tamás (1968-) (gyermekgyógyász)
Pályázati támogatás:TÁMOP-4.2.2.A-11/1/KONV-2012-0045
TÁMOP
Gyermekgyógyászat Kutatócsoport
Internet cím:DOI
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3.

001-es BibID:BIBFORM060757
Első szerző:Szabó Tamás (gyermekgyógyász)
Cím:Regulation of TRPC6 ion channels in podocytes : implications for focal segmental glomerulosclerosis and acquired forms of proteinuric diseases / T. Szabó, L. Ambrus, N. Zákány, Gy. Balla, T. Bíró
Dátum:2015
ISSN:0231-424X 1588-2683
Megjegyzések:The glomerular filtration barrier is a highly specialized tri-layer structure with unique functional properties. Podocyte dysfunction and cytoskeletal disorganization leads to disruption of the slit diaphragma, and proteinuria. Inflammatory diseases involving the kidney as well as inherited podocytopathies or diabetic nephropathy cause injury of the podocyte network. Focal segmental glomerulosclerosis (FSGS) is a pathologic entity that is a common cause of nephrotic syndrome with severe proteinuria in both adults and children. Several causative genes have been identified in the pathogenesis of FSGS. Mutations of the transient receptor potential canonical-6 (TRPC6), a non-selective cation channel that is directly activated by diacylglycerol (DAG), cause a particularly aggressive form of FSGS. Angiotensin II, acting through its AT1 receptor, plays a critical role in generation of proteinuria and progression of kidney injury in a number of kidney diseases, including FSGS. Mounting evidence suggest the central role of TRPC6 and perhaps other TRPC channels in the pathogenesis of FSGS as well as of acquired forms of proteinuria such as diabetic nephropathy or hypertension. Identification of signaling pathways downstream of TRPC6 may provide novel targets for the treatment of proteinuria and prevent progression of podocyte injury.
Tárgyszavak:Orvostudományok Klinikai orvostudományok idegen nyelvű folyóiratközlemény hazai lapban
proteinuric disease
focal segmental glomerulosclerosis (FSGS)
TRPC6
diabetic nephropathy
angiotensin II
podocyte
Megjelenés:Acta Physiologica Hungarica 102 : 3 (2015), p. 241-251. -
További szerzők:Ambrus Lídia (1986-) (élettanász) Zákány Nóra Balla György (1953-) (csecsemő és gyermekgyógyász, neonatológus) Bíró Tamás (1968-) (élettanász)
Pályázati támogatás:TÁMOP-4.2.2.A-11/1/KONV-2012-0045
TÁMOP
Gyermekgyógyászat Kutatócsoport
PD-76065
OTKA
Internet cím:Szerző által megadott URL
DOI
Intézményi repozitóriumban (DEA) tárolt változat
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