Abstract | AIMS/HYPOTHESIS: METHODS: Wild-type and Mkk3 (also known as Map2k3) gene-deficient db/db mice were assessed for the development of obesity, type 2 diabetes and renal injury from 8 to 32 weeks of age. RESULTS: Mkk3 (+/+) db/db and Mkk3 (-/-) db/db mice developed comparable obesity and were similar in terms of incidence and severity of type 2 diabetes. At 32 weeks, diabetic Mkk3 (+/+) db/db mice had increased kidney levels of phospho-p38 and MKK3 protein. In comparison, kidney levels of phospho-p38 in diabetic Mkk3 ( -/- ) db/db mice remained normal, despite a fourfold compensatory increase in MKK6 protein levels. The reduced levels of p38 MAPK signalling in the diabetic kidneys of Mkk3 ( -/- ) db/db mice was associated with protection against the following: declining renal function, increasing albuminuria, renal hypertrophy, podocyte loss, mesangial cell activation and glomerular fibrosis. Diabetic Mkk3 ( -/- ) db/db mice were also significantly protected from tubular injury and interstitial fibrosis, which was associated with reduced Ccl2 mRNA expression and interstitial macrophage accumulation. CONCLUSIONS/INTERPRETATION:
|
Authors | A K H Lim, D J Nikolic-Paterson, F Y Ma, E Ozols, M C Thomas, R A Flavell, R J Davis, G H Tesch |
Journal | Diabetologia
(Diabetologia)
Vol. 52
Issue 2
Pg. 347-58
(Feb 2009)
ISSN: 1432-0428 [Electronic] Germany |
PMID | 19066844
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
|
Chemical References |
- DNA Probes
- Receptors, Leptin
- Tumor Necrosis Factor-alpha
- leptin receptor, mouse
- p38 Mitogen-Activated Protein Kinases
- MAP Kinase Kinase 3
- Map2k3 protein, mouse
|
Topics |
- Aging
(genetics, physiology)
- Animals
- DNA Probes
- Diabetes Mellitus, Type 2
(enzymology, epidemiology, physiopathology)
- Diabetic Nephropathies
(enzymology, genetics, pathology)
- Hypertrophy
- Kidney
(injuries, pathology, physiopathology)
- MAP Kinase Kinase 3
(deficiency, genetics, metabolism)
- Mice
- Mice, Inbred Strains
- Mice, Knockout
- Mice, Obese
- Receptors, Leptin
(genetics)
- Tumor Necrosis Factor-alpha
(genetics)
- p38 Mitogen-Activated Protein Kinases
(metabolism)
|