How diabetes can favorize kidney fibrosis
One important clinical complication of diabetes is diabetic nephropathy, a severe condition leading to kidney fibrosis and preventing blood filtering. Under normal conditions, all cells of our body are supported by a scaffold called extracellular matrix. In the context of diabetic nephropathy, an excessive deposit of macromolecules that normally form the extracellular matrix occur; it is fibrosis.
Specific and effective treatments with low side-effects to prevent this pathological matrix accumulation are still lacking. A better understanding of how an excess of sugar in the blood can promote fibrosis in kidneys might open new therapeutic avenues.
Acetylation of integrin stimulates fibrosis
In a recent study published in Cells, scientists from Prof. Bernhard Wehrle-Haller group in collaboration with researchers from Princeton University have been able to unravel some of the physiological mechanisms stimulating fibrosis in the context of diabetes. Their experiments allowed to highlight the importance of a slight sugar-induced modification in a protein involved in extracellular matrix formation, the β1 integrin. An acetylation of this integrin appears to favorize fibrosis when glucose levels are high. β1 integrin helps cells to assemble the extracellular matrix and its acetylation induced by sugar increases matrix accumulation.
Acetylation of β1 integrin (left picture) favorizes fibrosis (in green) in mesangial cells grown during 16 h under high glucose concentrations in comparison to cells where β1 integrin is not acetylated (right picture).
Integrin acetylation forms the keystone to the understanding of kidney fibrosis development during diabetes. Targeting this key modification opens the way for more specific drugs able to redress the correct balance of extracellular matrix deposition with reduced side-effects in diabetic nephropathy. As an integrin binding site potentially contributes to the high infection rate of the new coronavirus causing covid-19, these recent findings might provide new avenues to fight covid-196 Apr 2020