Monocyte/Macrophage Polarisation in Diabetic Complications

Abstract

Diabetic nephropathy (DN), a complication of diabetes is the leading cause of chronic kidney disease and contributes strongly to the morbidity and mortality of diabetes. Macrophage infiltration into renal tissues is a primary contributing factor to DN onset and progression yet few studies have examined kidney macrophage phenotype in diabetes and DN onset and progression. In this thesis the expression of macrophage phenotype markers was examined in association with kidney disease development in a mouse model of diabetes. Monocyte inflammatory gene expression profile was also examined in people with or without diabetic complications. In diabetic mouse kidney tissue increased expression of pro-inflammatory MCP-1 at 5 weeks preceded that of the anti-inflammatory marker CD163 at 30 weeks of diabetes. These changes occurred prior to altered kidney fibrosis marker expression. Whilst requiring further investigation the presence of increased anti-inflammatory M2 macrophages in kidney prior to damage suggests, at least at this early stage of disease progression, a protective phenotype. In the human study, few differences in monocyte inflammatory gene profiles were observed. This lack of marked change suggests that alterations in function (i.e. infiltration to tissue) occur in response to the circulating diabetic milieu or to tissue damage. Further detailed studies are required to investigate the response of these monocytes to inflammatory stimuli.