Despite the most diligent efforts of those with T1D, perfect glucose control is seldom achieved with today’s tools. This can lead to an increased risk of a number of potential long-term complications, including kidney disease. The mechanisms underlying development of diabetic kidney disease are poorly understood. One feature of it is progressive fibrosis or scarring of the kidney which contributes to kidney damage and a loss of renal function. A better understanding of this process could identify novel targets for therapy to preserve and perhaps improve kidney function in those with diabetic kidney disease. In this study, researchers found that a protein, called ADAM17 that is activated in the kidney of a T1D mouse model and appears to be related to scarring in the kidney. Blocking the activation of this protein in the mouse model or in kidney cells in the lab could reduce certain features of fibrosis. The group also found that blocking ADAM17 also reduced the amount of another protein, called Nox4 that has been implicated in the progression of diabetic kidney disease. This study suggests a new mechanism by which high glucose can damage the kidney, and offers hope for a novel candidate therapeutic target for drug discovery and development efforts.
Ramifications for Individuals with T1D:
Diabetic kidney disease can be a devastating complication of T1D with serious consequences. At present the only strategies to prevent and slow diabetic kidney disease are the rigorous management of diabetes and blood pressure. Novel and specific therapies are urgently needed to address this, and the elucidation of disease mechanisms should reveal targets against which such therapies can be developed. This research is the first step towards developing such novel drug therapies.
JDRF partially funded this study via a grant to Dr. Hanna Abboud.
Investigators and Institutions:
Hanna Abboud and colleagues at the University of Texas Health Science Center, San Antonio.
Ford BM, Eid AA, and others. ADAM17 mediates Nox4 expression and NADPH oxidase activity in the kidney cortex of OVE26 mice. Am J Physiol Renal Physiol. 2013 May 15.
Potential Therapeutic Approach Identified For Treating And Preventing Diabetic Kidney Disease