Recent insights into diabetic renal injury from the db/db mouse model of type 2 diabetic nephropathy

被引：121

作者：

Tesch, G. H. ^{[1
,2
]}

Lim, A. K. H. ^{[1
,2
]}

机构：

[1] Monash Med Ctr, Dept Nephrol, Clayton, Vic 3168, Australia

[2] Monash Univ, Dept Med, Monash Med Ctr, Clayton, Vic, Australia

来源：

AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY | 2011年 / 300卷 / 02期

基金：

英国医学研究理事会;

关键词：

kidney; gene knockout; uninephrectomy; therapy; MESANGIAL MATRIX EXPANSION; AMELIORATES PROGRESSION; INTERSTITIAL FIBROSIS; SUPEROXIDE-DISMUTASE; LEPTIN RECEPTOR; GENE-EXPRESSION; TRANSGENIC MICE; KIDNEY-DISEASE; BLOOD-PRESSURE; BETA ANTIBODY;

D O I：

10.1152/ajprenal.00607.2010

中图分类号：

Q4 [生理学];

学科分类号：

071003 ;

摘要：

Tesch GH, Lim AK. Recent insights into diabetic renal injury from the db/db mouse model of type 2 diabetic nephropathy. Am J Physiol Renal Physiol 300: F301-F310, 2011. First published December 8, 2010; doi:10.1152/ajprenal.00607.2010.-The db/db mouse is the most widely used animal model of type 2 diabetic nephropathy. Recent studies have utilized genetic backcrossing with transgenic mouse strains to create novel db/db strains that either lack or overexpress specific genes. These novel strains [ICAM-1-/-, CCL2-/-, MKK3-/-, osteopontin-/-, plasminogen activator inhibitor-1 (PAI-1)-/-, endothelial nitric oxide synthase-/-, SOD-Tg, rCAT-Tg] have provided valuable insights into the molecular mechanisms which promote diabetic renal injury. In addition, surgical removal of one kidney has been shown to accelerate injury in the remaining kidney of diabetic db/db mice. A number of novel therapeutic agents have also been tested in db/db mice, including inhibitors of inflammation (chemokine receptor antagonists, anti-CCL2 RNA aptamer, anti-c-fms antibody); oxidative stress (oxykine, biliverdin); the renin-angiotensin-aldosterone system (aliskiren, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, eplerenone); advanced glycation end products (AGE; pyridoxamine, alagebrium, soluble AGE receptor); angiogenesis (NM-3, anti-CXCL12 RNA aptamer, soluble Flt-1); lipid accumulation (statins, farnesoid X receptor agonists, Omacor); intracellular signaling pathways (PKC-beta or JNK inhibitors); and fibrosis [transforming growth factor (TGF)-beta antibody, TGF-beta R kinase inhibitor, soluble betaglycan, SMP-534, CTGF-antisense oligonucleotide, mutant PAI-1, pirfenidone], which have identified potential therapeutic targets for clinical translation. This review summarizes the advances in knowledge gained from studies in genetically modified db/db mice and treatment of db/db mice with novel therapeutic agents.

引用

页码：F301 / F310

页数：10

共 65 条

[1] Abnormal p38 mitogen-activated protein kinase signalling in human and experimental diabetic nephropathy [J].

Adhikary, L ;

Chow, F ;

Nikolic-Paterson, DJ ;

Stambe, C ;

Dowling, J ;

Atkins, RC ;

Tesch, GH .

DIABETOLOGIA, 2004, 47 (07) :1210-1222

[2] The AGE inhibitor pyridoxamine inhibits lipemia and development of renal and vascular disease in Zucker obese rats [J].

Alderson, NL ;

Chachich, ME ;

Youssef, NN ;

Beattie, RJ ;

Nachtigal, M ;

Thorpe, SR ;

Baynes, JW .

KIDNEY INTERNATIONAL, 2003, 63 (06) :2123-2133

[3] Leptin regulates neointima formation after arterial injury through mechanisms independent of blood pressure and the leptin receptor/STAT3 signaling pathways involved in energy balance [J].

Bodary, Peter F. ;

Shen, Yuechun ;

Ohman, Miina ;

Bahrou, Kristina L. ;

Vargas, Fernando B. ;

Cudney, Sarah S. ;

Wickenheiser, Kevin J. ;

Myers, Martin G., Jr. ;

Eitzman, Daniel T. .

ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY, 2007, 27 (01) :70-76

[4]

BOWER G, 1980, LAB INVEST, V43, P333

[5] Attenuation of interstitial fibrosis and tubular apoptosis in db/db transgenic mice overexpressing catalase in renal proximal tubular cells [J].

Brezniceanu, Marie-Luise ;

Liu, Fang ;

Wei, Chih-Chang ;

Chenier, Isabelle ;

Godin, Nicolas ;

Zhang, Shao-Ling ;

Filep, Janos G. ;

Ingelfinger, Julie R. ;

Chan, John S. D. .

DIABETES, 2008, 57 (02) :451-459

[6] Evidence that the diabetes gene encodes the leptin receptor: Identification of a mutation in the leptin receptor gene in db/db mice [J].

Chen, H ;

Charlat, O ;

Tartaglia, LA ;

Woolf, EA ;

Weng, X ;

Ellis, SJ ;

Lakey, ND ;

Culpepper, J ;

Moore, KJ ;

Breitbart, RE ;

Duyk, GM ;

Tepper, RI ;

Morgenstern, JP .

CELL, 1996, 84 (03) :491-495

[7] Omacor®, n-3 polyunsaturated fatty acid, attenuated albuminuria and renal dysfunction with decrease of SREBP-1 expression and triglyceride amount in the kidney of type II diabetic animals [J].

Chin, Ho Jun ;

Fu, Yan Yan ;

Ahn, Jeong Myung ;

Na, Ki Young ;

Kim, Yon Su ;

Kim, Suhnggwon ;

Chae, Dong-Wan .

NEPHROLOGY DIALYSIS TRANSPLANTATION, 2010, 25 (05) :1450-1457

[8] Macrophages in mouse type 2 diabetic nephropathy: Correlation with diabetic state and progressive renal injury [J].

Chow, F ;

Ozols, E ;

Nikolic-Paterson, DJ ;

Atkins, RC ;

Tesch, GH .

KIDNEY INTERNATIONAL, 2004, 65 (01) :116-128

[9] Monocyte chemoattractant protein-1-induced tissue inflammation is critical for the development of renal injury but not type 2 diabetes in obese db/db mice [J].

Chow, F. Y. ;

Nikolic-Paterson, D. J. ;

Ma, F. Y. ;

Ozols, E. ;

Rollins, B. J. ;

Tesch, G. H. .

DIABETOLOGIA, 2007, 50 (02) :471-480

[10] Intercellular adhesion molecule-1 deficiency is protective against nephropathy in type 2 diabetic db/db mice [J].

Chow, FY ;

Nikolic-Paterson, DJ ;

Ozols, E ;

Atkins, RC ;

Tesch, GH .

JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY, 2005, 16 (06) :1711-1722

← 1 2 3 4 5 6 7 →