Abstract
Diabetic nephropathy (DN) is the leading cause of end-stage renal disease globally. The primary initiating mechanism in DN is hyperglycemia-induced vascular dysfunction, but its progression is due to different pathological mechanisms, including oxidative stress, inflammatory cells infiltration, inflammation and fibrosis. Macrophages (Mφ) accumulation in kidneys correlates strongly with serum creatinine, interstitial myofibroblast accumulation and interstitial fibrosis scores. However, whether or not Mφ polarization is involved in the progression of DN has not been adequately defined. The prevalence of the different phenotypes during the course of DN, the existence of hybrid phenotypes and the plasticity of these cells depending of the environment have led to inconclusive results. In the same sense the role of the different macrophage phenotype in fibrosis associated or not to DN warrants additional investigation into Mφ polarization and its role in fibrosis. Due to the association between fibrosis and the progressive decline of renal function in DN, and the role of the different phenotypes of Mφ in fibrosis, in this review we examine the role of macrophage phenotype control in DN and highlight the potential factors contributing to phenotype change and injury or repair in DN.
Highlights
Diabetic nephropathy (DN) is currently the most prevalent chronic kidney disease and the leading cause of end-stage renal disease in adults [1]
Due to the association between fibrosis and the progressive decline of renal function in DN, and the role of the different phenotypes of Mφ in fibrosis, in this review we examine the role of macrophage phenotype control in DN and highlight the potential factors contributing to phenotype change and injury or repair in DN
In diabetic db/db mice, it has been shown that macrophage accumulation and activation provokes glomerular and tubular damage, albuminuria, elevated plasma creatinine, renal fibrosis and kidney expression of Mφ chemokines [12]
Summary
Diabetic nephropathy (DN) is currently the most prevalent chronic kidney disease and the leading cause of end-stage renal disease in adults [1]. Mφ are considered an important source of tumor necrosis factor-alpha (TNF-α) and it is known that this cytokine does play a pivotal role in the development of DN In this sense, TNF-α levels in kidneys are increased in experimental animal models of DN [13,14] and conditional knockout of TNF-α in Mφ revealed a complete block of TNF-α expression in diabetes-induced models. This fibrosis appears to be largely due to increase cellular components and Mφ presence, which is followed by an increase in interstitial fibrillary collagen. We examine the role of Mφ phenotype in fibrosis development and highlight its implications for new therapeutic strategies
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