Macrophage Phenotype and Fibrosis in Diabetic Nephropathy

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.

Magnoflorine Ameliorates Inflammation and Fibrosis in Rats With Diabetic Nephropathy by Mediating the Stability of Lysine-Specific Demethylase 3A

“…Hyperglycemia and hyperfiltration contribute to morphological changes, such as mesangial expansion, ECM accumulation, and glomerulosclerosis with nodular mesangial lesion ( Chang and Chen, 2020 ). Moreover, fibrosis has the characteristics of excessive deposits of ECM that leads to the replacement of functional parenchyma by fibrotic tissue, and renal fibrosis is the commonest pathological process in chronic kidney disease ( Calle and Hotter, 2020 ). Therefore, the current study is conducted to uncover the mechanisms of MF in DN with the conclusion pronouncing that MF inhibits inflammatory response and fibrosis in DN progression via the KDM3A/TGIF1/TGF- β 1/Smad2/3 axis.…”

“…Diabetic nephropathy (DN), the major cause of chronic kidney disease, is characterized by albuminuria, lowered glomerular filtration rate, hypertension, and mesangial matrix expansion in addition to tubulointerstitial fibrosis ( Giralt-Lopez et al, 2020 ). The progression of DN has been suggested to attribute to various pathological mechanisms, including inflammation and fibrosis ( Calle and Hotter, 2020 ). The current therapeutic maneuver of diabetic patients focuses on glycemic control and antihypertensive/lipidlowering treatments; however, these involvements do not prevent the development of chronic kidney disease in most diabetic patients ( Rayego-Mateos et al, 2020 ).…”

Protective Effects of Two Safflower Derived Compounds, Kaempferol and Hydroxysafflor Yellow A, on Hyperglycaemic Stress-Induced Podocyte Apoptosis via Modulating of Macrophage M1/M2 Polarization

“…The primary initiating mechanism in DN is hyperglycemia-induced vascular dysfunction. However, its progression is due to different pathological mechanisms, including oxidative stress and inflammatory cell infiltration [ 27 ]. The growing evidence indicates that immunological and inflammatory mechanisms play an important role in the development and progression of DN [ 28 ].…”

Adenosine A2A and A3 Receptors as Targets for the Treatment of Hypertensive-Diabetic Nephropathy

“…Diabetic nephropathy (DN) is the primary cause of end-stage renal disease (ESRD) [ 12 ]. It courses with glomerular hyperfiltration and hypertrophy, basal membrane thickening, and mesangial matrix expansion, leading to glomerulosclerosis, persistent proteinuria, and decreased GFR [ 13 , 14 ]. Hypertension independently contributes to DN [ 12 ], coexists in most diabetic patients [ 15 ], as well as represents a major cause of ESRD [ 16 ].…”