Immune Cells and Inflammation in Diabetic Nephropathy

Abstract

Diabetic nephropathy (DN) is a serious complication of diabetes. At its core, DN is a metabolic disorder which can also manifest itself in terms of local inflammation in the kidneys. Such inflammation can then drive the classical markers of fibrosis and structural remodeling. As a result, resolution of immune-mediated inflammation is critical towards achieving a cure for DN. Many immune cells play a part in DN, including key members of both the innate and adaptive immune systems. While these cells were classically understood to primarily function against pathogen insult, it has also become increasingly clear that they also serve a major role as internal sensors of damage. In fact, damage sensing may serve as the impetus for much of the inflammation that occurs in DN, in a vicious positive feedback cycle. Although direct targeting of these proinflammatory cells may be difficult, new approaches that focus on their metabolic profiles may be able to alleviate DN significantly, especially since dysregulation of the local metabolic environment may well be responsible for triggering inflammation to begin with. In this review, the authors consider the metabolic profile of several relevant immune types and discuss their respective roles.

MicroRNA‐326‐3p ameliorates high glucose and ox‐LDL‐IC‐ induced fibrotic injury in renal mesangial cells by targeting FcγRIII

“…The underlying mechanism is complicated and multiple molecular signalling pathways are involved. The previous studies have revealed the involvement of immune system in the pathophysiology of diabetes, DKD and some other chronic diseases, the proinflammatory events have been found to be triggered by innate and adaptive immunity pathways . Elevated oxidative LDL in serum of patients with diabetes is immunogenic and has been found to be able to induce the production of autoantibody and then form the oxidative LDL immune complex.…”

“…The previous studies have revealed the involvement of immune system in the pathophysiology of diabetes, DKD and some other chronic diseases, the proinflammatory events have been found to be triggered by innate and adaptive immunity pathways. 7,8,25 Elevated oxidative LDL in serum of patients with diabetes is immunogenic and has been found to be able to induce the production of autoantibody and then form the oxidative LDL immune complex. Hypercholesterolaemia is a proinflammatory trigger through the formation of ox-LDL-IC, which enhances the activation of human immunity in DKD and other diabetic complications.…”

“…The pathogenesis of DKD has not been fully clarified despite lots of evidence recently have suggested that inflammation, oxidative stress and fibrosis as the key contributors . Besides, accumulating studies have shown that immunity also played an important role in DKD …”

“…5,6 Besides, accumulating studies have shown that immunity also played an important role in DKD. [7][8][9] Fcγ receptor III (FcγRIII), a transmembrane glycoprotein, is one of members of immunoglobulin superfamily, 10 which expresses in various types of cells, such as leukocytes, monocytes, macrophages and tissue resident cells including glomerular mesangial cells (GMCs). 11 Activated FcγRIII is a low affinity receptor that can recognize and bind to IgG or its complex, then induces phagocytosis, oxidative burst and release of cytokines.…”

High-Mobility Group Nucleosome-Binding Protein 1 Mediates Renal Fibrosis Correlating with Macrophages Accumulation and Epithelial-to-Mesenchymal Transition in Diabetic Nephropathy Mice Model

“…Macrophages are found in normal kidney and in increased numbers in diseased kidney, well recognized for their pathogenic role in kidney inflammation and fibrosis [14, 15]. Such an increase in the macrophage population has been correlated with the presence of interstitial fibrosis.…”