Macrophage phenotype and its relationship with renal function in human diabetic nephropathy

Zhang, Xiaoliang; Yang, Ying; Zhao, Yu

doi:10.1371/journal.pone.0221991

Cited by 42 publications

(41 citation statements)

References 39 publications

(48 reference statements)

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“…In addition to the Mϕ response to cytokine cues, other mechanisms have been determined. Zhang et al exposed that a triggering receptor expressed on myeloid cells 1 (TREM-1) modulates the Mϕ phenotype towards M1 under high-glucose in vitro conditions; in conjunction the expression of TREM-1 in the renal interstitium is significantly correlated with the DN progression in human renal biopsies [32]. A recent study has shown that pioglitazone, a peroxisome proliferator activated receptor γ (PPARγ) agonist, promotes the M2 polarization; although it indicated that the process was not mediated by PPARγ, pioglitazone treatment in M2 cells did increase the expression of vascular endothelial cell growth factor receptor-3 (VEGFR3) via a PPARγ-dependent pathway [33].…”

Section: Macrophage Phenotype and Fibrosismentioning

confidence: 99%

Macrophage Phenotype and Fibrosis in Diabetic Nephropathy

Calle

Hotter

2020

IJMS

121

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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.

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Section: Macrophage Phenotype and Fibrosismentioning

confidence: 99%

Macrophage Phenotype and Fibrosis in Diabetic Nephropathy

Calle

Hotter

2020

IJMS

121

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“…Increasingly, research has suggested that inflammation is a critical factor activated by metabolic, hyperglycaemic, AGEs [ 19 ] and haemodynamic derangements. Macrophages may be pivotal to this process and unexplained inflammatory cells are known to mediate kidney inflammation [ 20 – 22 ]. Research has shown that macrophage infiltration is closely involved in regulation of serum creatinine, proteinuria, and interstitial fibrosis [ 23 ].…”

Section: Discussionmentioning

confidence: 99%

TAB1 regulates glycolysis and activation of macrophages in diabetic nephropathy

Zeng

et al. 2020

Inflamm. Res.

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Objective and design Macrophages exhibit strong phenotypic plasticity and can mediate renal inflammation by polarizing into an M1 phenotype. They play a pivotal role in diabetic nephropathy (DN). Here, we have investigated the regulatory role of transforming growth factor β-activated kinase 1-binding protein 1 (TAB1) in glycolysis and activation of macrophages during DN. Methods TAB1 was inhibited using siRNA in high glucose (HG)-stimulated bone marrow-derived macrophages (BMMs) and lentiviral vector-mediated TAB1 knockdown was used in streptozotocin (STZ)-induced diabetic mice. Western blotting, flow cytometry, qRT-PCR, ELISA, PAS staining and immunohistochemical staining were used for assessment of TAB1/nuclear factor-κB (NF-κB)/hypoxia-inducible factor-1α (HIF-1α), iNOS, glycolysis, inflammation and the clinical and pathological manifestations of diabetic nephropathy. Results We found that TAB1/NF-κB/HIF-1α, iNOS and glycolysis were up-regulated in BMMs under HG conditions, leading to release of further inflammatory factors, Downregulation of TAB1 could inhibit glycolysis/polarization of macrophages and inflammation in vivo and in vitro. Furthermore, albuminuria, the tubulointerstitial damage index and glomerular mesangial expansion index of STZ-induced diabetic nephropathy mice were decreased by TAB1 knockdown. Conclusions Our results suggest that the TAB1/NF-κB/HIF-1α signaling pathway regulates glycolysis and activation of macrophages in DN.

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“…The connection between macrophage phenotype and its relationship with renal function and histological changes in human DKD has been extensively explored. It was demonstrated that there is a positive correlation between the M1/M2 differentiation state and the progress of DKD [ 38 ].…”

Section: Discussionmentioning

confidence: 99%

Protective Effects of Thalidomide on High-Glucose-Induced Podocyte Injury through In Vitro Modulation of Macrophage M1/M2 Differentiation

Liao

Zhang

et al. 2020

Journal of Immunology Research

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Objective. It has been shown that podocyte injury represents an important pathological basis that contributes to proteinuria and eventually leads to kidney failure. High glucose (HG) activates macrophage polarization, further exacerbating HG-induced podocyte injury. Our previous study on diabetic nephropathy rats indicated that thalidomide (Tha) has renoprotective properties. The present study explored the effects of Tha on mRNA and protein expressions of inducible nitric oxide synthase (iNOS), tumor necrosis factor- (TNF-) α, mannose receptor (CD206), and arginase- (Arg-) 1 in HG-activated macrophages. iNOS and TNF-α are established as markers of classically activated macrophage (M1). CD206 and Arg-1 are regarded as markers of alternatively activated macrophages (M2). During the experiment, the supernatants of (HG)-treated and (Tha)-treated macrophages, designated as (HG) MS and (Tha) MS, were simultaneously collected and processed. TNF-α and interleukin- (IL-) 1β levels as well as protein expressions of nephrin and podocin in HG, (HG) MS, and (Tha) MS-cultured podocytes were evaluated. The results showed that compared to the 11.1 mM normal glucose (NG), the 33.3 mM HG-cultured RAW 264.7 cells exhibited upregulated iNOS and TNF-α mRNAs and protein expressions, and downregulated CD206 and Arg-1 expressions significantly (p<0.05). Tha 200 μg/ml suppressed iNOS and TNF-α, and promoted CD206 and Arg-1 expressions significantly compared to the HG group (p<0.05). Furthermore, (HG) MS-treated podocytes showed an increase in TNF-α and IL-1β levels and a downregulation in nephrin and podocin expression significantly compared to NG-treated and HG-treated podocytes (p<0.05). The (Tha 200 μg/ml) MS group exhibited a decrease in TNF-α and IL-1β level, and an upregulation in nephrin and podocin expressions significantly compared to the (HG) MS group (p<0.05). Our research confirmed that HG-activated macrophage differentiation aggravates HG-induced podocyte injury in vitro and the protective effects of Tha might be related to its actions on TNF-α and IL-1β levels via its modulation on M1/M2 differentiation.

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Macrophage phenotype and its relationship with renal function in human diabetic nephropathy

Cited by 42 publications

References 39 publications

Macrophage Phenotype and Fibrosis in Diabetic Nephropathy

Macrophage Phenotype and Fibrosis in Diabetic Nephropathy

TAB1 regulates glycolysis and activation of macrophages in diabetic nephropathy

Protective Effects of Thalidomide on High-Glucose-Induced Podocyte Injury through In Vitro Modulation of Macrophage M1/M2 Differentiation

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