The Role of Macrophages in Kidney Fibrosis

Wang, Xiaoling; Chen, Jianwei; Xu, Jun; Xie, Jun; Harris, David C.H.; Zheng, Guoping

doi:10.3389/fphys.2021.705838

Cited by 66 publications

(85 citation statements)

References 121 publications

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“…Previous results on the role of the innate immunity system in post-infarction myocardial regeneration in humans and animals [8,10,11] and its place in cardiorenal interactions in animals provided the rationale for studying this issue [6,7,12,13]. Involvement of monocytes/macrophages in both the inflammatory and regenerative phases of post-infarction myocardial remodeling has already been confirmed by the presence of their prolonged CD68+, CD163+, CD206+ and stabilin-1+ macrophage infiltration in both IA and non-IA of the myocardium in patients who experienced a fatal MI [10].…”

Section: Discussionmentioning

confidence: 99%

Macrophages of the “Heart-Kidney” Axis: Their Dynamics and Correlations with Clinical Data and Outcomes in Patients with Myocardial Infarction

Kercheva

Ryabov

Gombozhapova

et al. 2022

JPM

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Changes in the macrophage infiltration of kidneys in rodents under ischemic conditions may affect cardiac macrophages and lead to development of adaptive cardiac remodeling. The aim of our study was to translate experimental findings into clinically relevant applications and assess the features of macrophage infiltration of the kidney and its correlations with changes in macrophage infiltration of the myocardium and with clinical data in patients who experienced a fatal myocardial infarction (MI). We examined fragments of both organs taken from patients (n = 30) who suffered from fatal MI. Macrophage infiltration was assessed by immunohistochemistry. Macrophage infiltration of the kidneys in patients with fatal MI is heterogeneous. The early period of MI was shown to be characterized by the prevalence of CD163+ and CD68+ cells, and in the long-term period by only CD163+ cells. However, only the level of CD206+ cells in the kidneys showed the dynamics representing the late MI period. Its decrease accompanied increase in the numbers of cardiac CD68+, CD163+, CD206+, and stabilin-1+ cells in the infarct area. Kidney CD206+ cells had more correlations with cardiac macrophages than other cells, and the presence of these cells also correlated with impairment of renal function and early death.

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Section: Discussionmentioning

confidence: 99%

Macrophages of the “Heart-Kidney” Axis: Their Dynamics and Correlations with Clinical Data and Outcomes in Patients with Myocardial Infarction

Kercheva

Ryabov

Gombozhapova

et al. 2022

JPM

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“…Unexpectedly, macrophage and monocyte accumulation was reduced by chemokine treatment, whereas it was aggravated by blockade of CCL9, although without significant impact on the ratio of M2 to M1 macrophages. Monocytes and pro-inflammatory M1 macrophages are well-known to contribute to ongoing kidney inflammation and damage [ 27 ]. Moreover, although M2 macrophages can mediate anti-inflammatory effects upon acute kidney injury, they contribute to CKD by promoting kidney fibrosis and increasingly accumulate in the injured kidney during CKD development [ 27 , 28 , 29 , 30 , 31 ].…”

Section: Discussionmentioning

confidence: 99%

Chemokine CCL9 Is Upregulated Early in Chronic Kidney Disease and Counteracts Kidney Inflammation and Fibrosis

et al. 2022

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Inflammation and fibrosis play an important pathophysiological role in chronic kidney disease (CKD), with pro-inflammatory mediators and leukocytes promoting organ damage with subsequent fibrosis. Since chemokines are the main regulators of leukocyte chemotaxis and tissue inflammation, we performed systemic chemokine profiling in early CKD in mice. This revealed (C-C motif) ligands 6 and 9 (CCL6 and CCL9) as the most upregulated chemokines, with significantly higher levels of both chemokines in blood (CCL6: 3–4 fold; CCL9: 3–5 fold) as well as kidney as confirmed by Enzyme-linked Immunosorbent Assay (ELISA) in two additional CKD models. Chemokine treatment in a mouse model of early adenine-induced CKD almost completely abolished the CKD-induced infiltration of macrophages and myeloid cells in the kidney without impact on circulating leukocyte numbers. The other way around, especially CCL9-blockade aggravated monocyte and macrophage accumulation in kidney during CKD development, without impact on the ratio of M1-to-M2 macrophages. In parallel, CCL9-blockade raised serum creatinine and urea levels as readouts of kidney dysfunction. It also exacerbated CKD-induced expression of collagen (3.2-fold) and the pro-inflammatory chemokines CCL2 (1.8-fold) and CCL3 (2.1-fold) in kidney. Altogether, this study reveals for the first time that chemokines CCL6 and CCL9 are upregulated early in experimental CKD, with CCL9-blockade during CKD initiation enhancing kidney inflammation and fibrosis.

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“…αSMA is a commonly used biomarker for myofibroblast, which plays a critical role in tissue fibrosis. 23,24 We found that the number of F4/ 80 + αSMA + MMT cells was decreased after GW2580 treatment when compared with the vehicle group (Figures 4B and 5). Our results suggested that GW2580 treatment could attenuate bladder fibrosis by partially inhibiting F4/80 + αSMA + MMT cells.…”

mentioning

confidence: 85%

The preventive effects of colony‐stimulating factor 1 receptor (CSF‐1R) inhibition on bladder outlet obstruction induced remodeling

Wang

Sun

Gao

et al. 2022

Neurourology and Urodynamics

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Introduction Bladder outlet obstruction (BOO) is a common problem that can affect bladder structure and function. Currently, there is no effective drugs available to prevent BOO‐induced remodeling. Previous reports have demonstrated that the pathogenesis of BOO is associated with macrophage infiltration and polarization, which is physiologically dependent on colony‐stimulating factor 1 receptor (CSF‐1R) activation. Here we utilized a highly selective CSF‐1R inhibitor, GW2580, to determine its preventive effects on BOO‐induced remodeling. Methods A total of 24 Sprague–Dawley rats were randomly divided into sham, BOO + vehicle, and BOO + GW2580 group. GW2580 or vehicle control was administrated by oral gavage at daily doses of 40 mg/kg for 6 weeks. Bladder samples were collected for histopathology, immunohistochemistry, immunofluorescence, western blotting, and flow cytometry analysis. Results Our results demonstrated that bladder fibrosis was ameliorated by GW2580 compared with the vehicle group (22.01% ± 5.13% vs. 32.15% ± 7.24%, p < 0.01). Furthermore, treatment with GW2580 induced an inhibition of macrophage infiltration (4.41% ± 1.28% vs. 13.57% ± 3.42%, p < 0.001) and M2 macrophage polarization (10.67% ± 4.15% vs. 28.59% ± 6.38%, p < 0.001). There was also a decrease of profibrotic F4/80+ α‐smooth muscle actin+ (α‐SMA+) macrophage to myofibroblast transition (9.11% ± 2.58% vs. 17.33% ± 4.01%, p < 0.001) and CD163+TGF‐β1+ cells (7.68% ± 2.10% vs. 14.17% ± 4.09%, p < 0.01) in the GW2580 group when compared with the vehicle group. Conclusions In summary, our findings showed that GW2580 is a worthwhile candidate for a follow‐up study to test in the treatment of BOO‐induced remodeling.

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The Role of Macrophages in Kidney Fibrosis

Cited by 66 publications

References 121 publications

Macrophages of the “Heart-Kidney” Axis: Their Dynamics and Correlations with Clinical Data and Outcomes in Patients with Myocardial Infarction

Macrophages of the “Heart-Kidney” Axis: Their Dynamics and Correlations with Clinical Data and Outcomes in Patients with Myocardial Infarction

Chemokine CCL9 Is Upregulated Early in Chronic Kidney Disease and Counteracts Kidney Inflammation and Fibrosis

The preventive effects of colony‐stimulating factor 1 receptor (CSF‐1R) inhibition on bladder outlet obstruction induced remodeling

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