Impact of the Hypoxia-Inducible Factor-1 α (HIF1A) Pro582Ser Polymorphism on Diabetes Nephropathy

被引：62

作者：

Gu, Harvest F. ^{[1
]}

Zheng, Xiaowei ^{[1
]}

Abu Seman, Norhashimah ^{[1
,2
]}

Gu, Tianwei ^{[1
]}

Botusan, Ileana Ruxandra ^{[1
]}

Sunkari, Vivekananda Gupta ^{[1
]}

Lokman, Ezarul Faradianna ^{[1
,2
]}

Brismar, Kerstin ^{[1
]}

Catrina, Sergiu-Bogdan ^{[1
]}

机构：

[1] Karolinska Inst, Karolinska Univ Hosp, Dept Mol Med & Surg, Rolf Luft Res Ctr Diabet & Endocrinol, Stockholm, Sweden

[2] Inst Med Res, Cardiovasc Diabet & Nutr Res Ctr, Kuala Lumpur 50588, Malaysia

来源：

DIABETES CARE | 2013年 / 36卷 / 02期

基金：

瑞典研究理事会;

关键词：

CREB-BINDING PROTEIN; FACTOR-1-ALPHA GENE; KIDNEY-DISEASE; RENAL INJURY; DB/DB MICE; TRANSACTIVATION; MODEL; SUSCEPTIBILITY; IDENTIFICATION; HYDROXYLATION;

D O I：

10.2337/dc12-1125

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

OBJECTIVE-Hypoxia plays a major pathogenic role in diabetic nephropathy (DN). We have investigated in this study the effect of hypoxia-inducible factor 1 alpha subunit (HIF1A) genetic polymorphisms on the development of DN. RESEARCH DESIGN AND METHODS-In 1,165 American type 1 diabetic patients with and without DN selected from the Genetics of Kidneys in Diabetes (GoKinD) study, the HIF1A genetic polymorphisms were genotyped with TaqMan allelic discrimination. The regulation of HIF-1 alpha in the kidneys of diabetic mice was appreciated by immunohistochemistry, and the effect HIF1A Pro582Ser polymorphism on HIF-1 alpha sensitivity to glucose was evaluated in vitro. RESULTS-We identified a protective association between HIF1A Pro582Ser polymorphism and DN in male subjects. We also provided mechanistic insights that HIF-1 alpha is repressed in the medulla of diabetic mice despite hypoxia and that Pro582Ser polymorphism confers less sensitivity to the inhibitory effect of glucose during a hypoxic challenge. CONCLUSIONS-The current study demonstrates for the first time that HIF1A Pro582Ser polymorphism has an effect on DN, possibly by conferring a relative resistance to the repressive effect of glucose on HIF-1 alpha. Diabetes Care 36:415-421, 2013

引用

页码：415 / 421

页数：7

共 33 条

[1] Regulation of hypoxia-inducible factor 1 and the loss of the cellular response to hypoxia in diabetes [J].

Bento, C. F. ;

Pereira, P. .

DIABETOLOGIA, 2011, 54 (08) :1946-1956

[2] The Chaperone-Dependent Ubiquitin Ligase CHIP Targets HIF-1α for Degradation in the Presence of Methylglyoxal [J].

Bento, Carla Figueira ;

Fernandes, Rosa ;

Ramalho, Jose ;

Marques, Carla ;

Shang, Fu ;

Taylor, Allen ;

Pereira, Paulo .

PLOS ONE, 2010, 5 (11)

[3] Deletion of the von Hippel-Lindau gene in pancreatic β cells impairs glucose homeostasis in mice [J].

Cantley, James ;

Selman, Colin ;

Shukla, Deepa ;

Abramov, Andrey Y. ;

Forstreuter, Frauke ;

Esteban, Miguel A. ;

Claret, Marc ;

Lingard, Steven J. ;

Clements, Melanie ;

Harten, Sarah K. ;

Asare-Anane, Henry ;

Batterham, Rachel L. ;

Herrera, Pedro L. ;

Persaud, Shanta J. ;

Duchen, Michael R. ;

Maxwell, Patrick H. ;

Withers, Dominic J. .

JOURNAL OF CLINICAL INVESTIGATION, 2009, 119 (01) :125-135

[4] Redox-regulated recruitment of the transcriptional coactivators CREB-binding protein and SRC-1 to hypoxia-inducible factor 1α [J].

Carrero, P ;

Okamoto, K ;

Coumailleau, P ;

O'Brien, S ;

Tanaka, H ;

Poellinger, L .

MOLECULAR AND CELLULAR BIOLOGY, 2000, 20 (01) :402-415

[5] Hyperglycentia regulates hypoxia-inducible factor-1α protein stability and function [J].

Catrina, SB ;

Okamoto, K ;

Pereira, T ;

Brismar, K ;

Poellinger, L .

DIABETES, 2004, 53 (12) :3226-3232

[6] Testosterone replacement therapy promotes angiogenesis after acute myocardial infarction by enhancing expression of cytokines HIF-1a, SDF-1a and VEGF [J].

Chen, Yeping ;

Fu, Lu ;

Han, Ying ;

Teng, Yueqiu ;

Sun, Junfeng ;

Xie, Rongsheng ;

Cao, Junxian .

EUROPEAN JOURNAL OF PHARMACOLOGY, 2012, 684 (1-3) :116-124

[7] Polymorphisms in hypoxia inducible factor 1 and the initial clinical presentation of coronary disease [J].

Hlatky, Mark A. ;

Quertermous, Thomas ;

Boothroyd, Derek B. ;

Priest, James R. ;

Glassford, Alec J. ;

Myers, Richard M. ;

Fortmann, Stephen P. ;

Iribarren, Carlos ;

Tabor, Hory K. ;

Assimes, Themistocles L. ;

Tibshirani, Robert J. ;

Go, Alan S. .

AMERICAN HEART JOURNAL, 2007, 154 (06) :1035-1042

[8] High glucose activates HIF-1-mediated signal transduction in glomerular mesangial cells through a carbohydrate response element binding protein [J].

Isoe, Tsubasa ;

Makino, Yuichi ;

Mizumoto, Katsutoshi ;

Sakagami, Hidemitsu ;

Fujita, Yukihiro ;

Honjo, Jun ;

Takiyama, Yumi ;

Itoh, Hiroshi ;

Haneda, Masakazu .

KIDNEY INTERNATIONAL, 2010, 78 (01) :48-59

[9] HIFα targeted for VHL-mediated destruction by proline hydroxylation:: Implications for O2 sensing [J].

Ivan, M ;

Kondo, K ;

Yang, HF ;

Kim, W ;

Valiando, J ;

Ohh, M ;

Salic, A ;

Asara, JM ;

Lane, WS ;

Kaelin, WG .

SCIENCE, 2001, 292 (5516) :464-468

[10] Targeting of HIF-α to the von Hippel-Lindau ubiquitylation complex by O2-regulated prolyl hydroxylation [J].

Jaakkola, P ;

Mole, DR ;

Tian, YM ;

Wilson, MI ;

Gielbert, J ;

Gaskell, SJ ;

von Kriegsheim, A ;

Hebestreit, HF ;

Mukherji, M ;

Schofield, CJ ;

Maxwell, PH ;

Pugh, CW ;

Ratcliffe, PJ .

SCIENCE, 2001, 292 (5516) :468-472

← 1 2 3 4 →