Collagen Deposition in Diabetic Kidney Disease Boosts Intercellular Signaling: A Mathematical Model

Abstract

ABSTRACTDiabetic kidney disease is a health burden that is becoming more prevalent in the US and worldwide. The limited options for treating and preventing diabetic kidney disease are in part due to gaps in our understanding of the progression of diabetic kidney damage and its impacts on cellular function. An important cellular function in the kidney glomerulus is intercellular communication via the release and uptake of soluble cytokines and growth factors. In diabetic kidney disease, excess collagen deposition alters the mesangial matrix properties, which, we hypothesize, diminishes the intercellular signaling between key glomerular cells. To test our hypothesis, we utilized established mathematical models of transport to study the impact of pathological deposition on the ability of cells to communicate via intercellular signaling. Our analysis reveals that pathological collagen deposition can enhance the signaling range of the glomerular cells rather than diminishing it.SIGNIFICANCEThe incidence of diabetes is expected to rise to over 600 million by the year 2040, one third of whom are expected to develop diabetic kidney disease. Our lack of understanding of how diabetic kidney disease progresses and affects cellular and tissue function has led to our inability to mitigate the rapidly rising burden of diabetic kidney disease. A hallmark of diabetic kidney damage is collagen deposition, yet its impact on cellular and tissue function is still not well understood. The elucidation of the impact of collagen deposition on cellular and tissue function will enable the identification of mechanisms that exacerbate the progression of diabetic kidney damage and thus provide novel avenues for preventing or slowing the progression of diabetic kidney damage.