2010
Functional analysis of the common haplotype in the Receptor for Advanced Glycation End-products gene previously identified as a susceptibility factor for diabetic nephropathy
KAŇKOVÁ, Kateřina, Petr BENEŠ a Šárka KUCHTÍČKOVÁZákladní údaje
Originální název
Functional analysis of the common haplotype in the Receptor for Advanced Glycation End-products gene previously identified as a susceptibility factor for diabetic nephropathy
Název česky
Functional analysis of the common haplotype in the Receptor for Advanced Glycation End-products gene previously identified as a susceptibility factor for diabetic nephropathy
Autoři
KAŇKOVÁ, Kateřina (203 Česká republika, garant), Petr BENEŠ (203 Česká republika) a Šárka KUCHTÍČKOVÁ (203 Česká republika)
Vydání
Experimental and Clinical Endocrinology & Diabetes, Germany, Thieme, 2010, 0947-7349
Další údaje
Jazyk
angličtina
Typ výsledku
Článek v odborném periodiku
Obor
30202 Endocrinology and metabolism
Stát vydavatele
Německo
Utajení
není předmětem státního či obchodního tajemství
Impakt faktor
Impact factor: 1.826
Kód RIV
RIV/00216224:14110/10:00040436
Organizační jednotka
Lékařská fakulta
UT WoS
000275138500005
Klíčová slova česky
RAGE; hyperglycemia; transcriptional activity; haplotype; reporter assay
Klíčová slova anglicky
RAGE; hyperglycemia; transcriptional activity; haplotype; reporter assay
Příznaky
Mezinárodní význam, Recenzováno
Změněno: 16. 3. 2010 14:39, prof. MUDr. Kateřina Kaňková, Ph.D.
V originále
The Receptor for Advanced Glycation End-products (RAGE) belongs to the family of pattern-recognition receptors and is significantly involved in the molecular mechanisms mediating pro-inflammatory action of hyperglycemia in diabetes. The aim of the current study was to elucidate the possible functional impact of the genetic variability in the AGER gene constituting previously identified risk haplotype for diabetic nephropathy (-429C/-374T/2184G) by testing the haplotype-specific effect on the AGER gene transcriptional activity in vitro. Promotor and intron 8 constructs carrying respective substitutions were amplified and cloned into pGL3-Basic reporter vector and subsequently used for transfection of HEK293 cells. Following 48hrs incubation in either normo- (5 mM/L) or hyperglycemic (25 mM/L) culture medium luciferase activity was measured to assess transcriptional efficiency. Risk haplotype was associated with the highest transcriptional activity in hyperglycemia and greatest relative increase of activity between normo- and hyperglycemia conditions (approx. 3-times). We conclude that ascertained functional differences in the regulatory regions of the AGER gene might have significant consequences for the development of hyperglycemia-related pathology in diabetics.
Česky
The Receptor for Advanced Glycation End-products (RAGE) belongs to the family of pattern-recognition receptors and is significantly involved in the molecular mechanisms mediating pro-inflammatory action of hyperglycemia in diabetes. The aim of the current study was to elucidate the possible functional impact of the genetic variability in the AGER gene constituting previously identified risk haplotype for diabetic nephropathy (-429C/-374T/2184G) by testing the haplotype-specific effect on the AGER gene transcriptional activity in vitro. Promotor and intron 8 constructs carrying respective substitutions were amplified and cloned into pGL3-Basic reporter vector and subsequently used for transfection of HEK293 cells. Following 48hrs incubation in either normo- (5 mM/L) or hyperglycemic (25 mM/L) culture medium luciferase activity was measured to assess transcriptional efficiency. Risk haplotype was associated with the highest transcriptional activity in hyperglycemia and greatest relative increase of activity between normo- and hyperglycemia conditions (approx. 3-times). We conclude that ascertained functional differences in the regulatory regions of the AGER gene might have significant consequences for the development of hyperglycemia-related pathology in diabetics.
Návaznosti
| KJB501620601, projekt VaV |
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