AsianScientist (Nov. 16, 2018) – A team of scientists at the Duke-National University of Singapore Medical School, Singapore, have genetically engineered mice that emulate diabetic nephropathy, a severe form of kidney damage in humans with diabetes. They published their results in Diabetes.
Kidney damage in people with diabetes can lead to life-threatening kidney failure. In Singapore, diabetes is the leading cause of end-stage kidney disease requiring dialysis. There are strong ethnic and familial associations for kidney disease in diabetes, indicating a role of genetic factors in determining susceptibility.
Mouse models that recapitulate the features of kidney disease seen in humans have been immensely useful for identifying its root causes, as well as improving diagnosis and treatment for diabetics who have kidney complications. However, diabetic mice typically only develop minimal kidney damage.
In the present study, researchers led by Professor Thomas Coffman, dean of the Duke-NUS Medical School, developed a mouse model that combines type 1 diabetes with over-activation of a hormone system called the renin-angiotensin system. The latter is known to be overly activated in humans with diabetic kidney disease.
When the researchers analyzed the genes expressed in the filtering units—or glomeruli—of these mice, they found that clusters of genes associated with activation of the immune system and inflammatory responses were expressed in the susceptible strain of mice, but not expressed in the control strain.
“Our data suggest that inflammation and immune responsiveness may be critical features in determining susceptibility to kidney disease in diabetes,” said Coffman.
As there are a number of available drugs for inhibiting the immune system and inflammation, the findings suggest that the development of diabetic nephropathy can be prevented or slowed by targeting inflammatory pathways.
“Although the precise genetic determinants of susceptibility and resistance to diabetic nephropathy may differ between mice and humans, it is likely that the molecular pathways involved are similar,” the researchers added. “Such pathways are attractive as biomarkers for disease susceptibility and targets for therapy.”
The article can be found at: Gurley et al. (2018) Inflammation and Immunity Pathways Regulate Genetic Susceptibility to Diabetic Nephropathy.
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Source: National University of Singapore; Photo: Shutterstock.
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