Polarized M2c macrophages have a promoting effect on the epithelial-to-mesenchymal transition of human renal tubular epithelial cells

Zhao, Chen; Dong, Feihong; Lu, Jiamei; Wei, Linting; Tian, Liang; Ge, Heng; Zou, Yixin; Ma, Xiaoqin; Yang, Yanyan; Zhou, Lin; Han, Jin Soo; Fu, Rongguo; Wang, Li

doi:10.1016/j.imbio.2018.08.008

Cited by 10 publications

(12 citation statements)

References 29 publications

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“…The signature molecules of M2b macrophages include CD86, CD206, and MHCII, and they can secrete IL-10, TNF- α , IL-1 β, and IL-6 [ 15 , 23 ]. Markers of M2c include CD163, CD206, MERTK, and CXCL13, and these cells can secrete IL-10 and TGF- β and are simultaneously activated by IL-10 and glucocorticoids [ 12 , 14 , 24 ].…”

Section: Discussionmentioning

confidence: 99%

“…For example, M2a participates in Th2 reaction and allergic reactions and can kill parasites, while M2b is involved in immune regulation. M2c has a de-priming effect and can secrete various antiinflammatory cytokines, which are mainly involved in tissue remodeling and matrix deposition [14][15][16]. However, the role of macrophage subtypes in the pathogenesis of sJIA has not been thoroughly investigated so far.…”

Section: Introductionmentioning

confidence: 99%

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Significance of Macrophage Subtypes in the Peripheral Blood of Children with Systemic Juvenile Idiopathic Arthritis

et al. 2021

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Introduction: Symptomatic juvenile idiopathic arthritis (sJIA) is an autoinflammatory disease, and monocytes/macrophages play an important role. However, which macrophage subtype plays a major role in different stages of sJIA is still unclear. This study aimed to explore macrophage subtypes in different stages of sJIA. Methods: Twenty-two children with sJIA who were followed up at Shanghai Children's Hospital from January 2018 to December 2020 were enrolled in this study. sJIA children were divided into an activity group (n = 12) and an inactivity group (n = 10). In the activity group, subjects with newly diagnosed sJIA and untreated were included; in the inactivity group, subjects with inactive sJIA meeting the 2011 ACR criteria for sJIA were recruited. Ten children with orthostatic proteinuria served as controls. Peripheral blood was collected. Flow cytometry was performed to detect macrophage subtypes: M1 (CD14 ? CD86 ? CD80 ? ), M2a (CD14 ? CD206 ? CD301 ? ), M2b (CD14 ? CD206 ? CD86 ? ) and M2c (CD14 ? CD206 ? CD163 ? ), and the contents of cytokines were also examined, including interleukins (IL) (IL-1b, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10 and IL-17), interferon-a, interferon-c, and tumor necrosis-a. Results: M1 marker CD80 and M2 marker CD163, CD301 were highly expressed in children with active sJIA. The majority of macrophages were M1 and M2a in the activity group (P \ 0.05). In the inactivity group, M2 tended to polarize into M2b and M2c (P \ 0.05). IL-6 significantly increased in the activity group (P \ 0.05), while IL-10, IL-4 and IL-17 markedly increased in the inactivity group (P \ 0.05). Conclusions: In the active sJIA, M1 activation promotes inflammation, while M2a rapidly responds to inhibit inflammation; in the inactive sJIA, M2b and M2c play a major role in inhibiting inflammation.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Significance of Macrophage Subtypes in the Peripheral Blood of Children with Systemic Juvenile Idiopathic Arthritis

et al. 2021

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“…Relatedly, we demonstrated that u-sCD163 levels were higher in patients with severe tubule-interstitial lesions, while being significantly correlated with global glomerulosclerosis and segmental glomerulosclerosis score. In vitro experiments indicated that incubation of human renal proximal tubular epithelial cells (HK-2) with M2c macrophages promoted epithelial-to mesenchymal transition (EMT) of HK-2 cells ( 22 ). In a single-cell atlas of mouse model of unilateral ureteral obstruction (UUO), monocytes recruited to the kidney early after injury rapidly adopt a proinflammatory, profibrotic phenotype that expresses Arg1 + M2 macrophages ( 23 ).…”

Section: Discussionmentioning

confidence: 99%

Urinary Soluble CD163 Levels Predict IgA Nephropathy Remission Status

et al. 2021

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Noninvasive biomarkers of disease activity are needed to predict disease remission status in patients with IgA nephropathy (IgAN). Soluble CD163 (sCD163), shed by monocytes and macrophages, is a potential biomarker in diseases associated with excessive macrophage activation. We investigated the association of urinary sCD163 (u-sCD163) with histopathological activity and clinical manifestations in 349 patients with biopsy-diagnosed IgAN. U-sCD163 was measured via enzyme-linked immunosorbent assay. In patients with IgAN, higher u-sCD163 levels were associated with histological lesions of greater severity, as well as more proteinuria and poorer renal function. Additionally, u-sCD163 was correlated with infiltration of tubulointerstitial CD163+ macrophages. High u-sCD163 levels (>3.57 ng/mg Cr) were associated with a 2.66-fold greater risk for IgAN remission failure in adjusted analyses. Adding u-sCD163 levels to the model containing clinical data at biopsy and MEST-C score significantly improved the risk prediction of IgAN remission status (AUC 0.788). Together, our results suggest that u-sCD163 may be a useful noninvasive biomarker to evaluate disease severity and remission status of IgAN.

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“…Human monocytic leukaemia cell line THP-1 cells in logarithmic growth phase were collected to prepare cell suspension, and the cells concentration was adjusted to 5 × 10 5 cells/mL. The cells were inoculated with 1 × 10 6 cells per well in 6-well plates containing RPMI-1640 medium, 1% FBS, and 200 ng/ml phorbol 12-myristate 13-acetate (PMA, Sigma Aldrich, USA) for 12 h. These cells were then treated with 20 ng/ml IL-10 for 0 h, 12 h, and 24 h [ 19 ]. The mRNA expressions of iNOS, CD163, and CD206 were detected by RT-qPCR to verify the induction of M2c macrophages.…”

Section: Methodsmentioning

confidence: 99%

“…It has been confirmed that infiltrating macrophages is related to the degree and severity of renal fibrosis [ 18 ]. Cell coculture experiments found that M2c macrophages can promote the EMT process of renal tubular epithelial cells [ 19 ]. TGF- β 1 is a multifunctional cytokine that plays a fundamental role in regulating renal fibrosis.…”

Section: Introductionmentioning

confidence: 99%

Jieduquyuzishen Prescription Attenuates Renal Fibrosis in MRL/lpr Mice via Inhibiting EMT and TGF-β1/Smad2/3 Pathway

Fan³

et al. 2022

Evidence-Based Complementary and Alternative Medicine

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Jieduquyuziyin prescription (JP) has been used to treat lupus nephritis (LN) and its effectiveness in the treatment of LN has been clinically proven, but the underlying mechanisms have yet to be completely understood. This aim of this study was to clarify the efficacy of JP on the epithelial-mesenchymal transition (EMT) of renal tubular epithelial cells and the molecular mechanisms of JP in MRL/lpr mice. In vivo, we observed the therapeutic actions of JP in MRL/lpr mice as well as its antifibrosis effect and potential mechanism. In vitro, we evaluated the role of JP in EMT and its possible mechanism through the EMT of human renal proximal tubular epithelial cells (HK-2) induced by transforming growth factor-beta 1 (TGF-β1) and M2c macrophages. HK-2 cells were treated with JP-treated serum, and MRL/lpr mice were treated by JP for 8 weeks. The results showed that JP alleviated disease activity, improved renal function, decreased proteinuria, and improved renal injury and fibrosis in MRL/lpr mice. Furthermore, JP suppressed the activation of the TGF-β1/Smad2/3 signaling pathway, upregulated the E-cadherin levels, and downregulated the Vimentin and mesenchymal α-smooth muscle actin (α-SMA) levels in the kidney of MRL/lpr mice. JP was further found to prevent the TGF-β1 and M2c macrophages-induced EMT of HK-2 cells. Collectively, JP could alleviate the disease activity of MRL/lpr mice, improve renal function, and attenuate renal fibrosis, and its underlying mechanisms may be related to the inhibition of EMT and TGF-β1/Smad2/3 signaling pathway.

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Polarized M2c macrophages have a promoting effect on the epithelial-to-mesenchymal transition of human renal tubular epithelial cells

Cited by 10 publications

References 29 publications

Significance of Macrophage Subtypes in the Peripheral Blood of Children with Systemic Juvenile Idiopathic Arthritis

Significance of Macrophage Subtypes in the Peripheral Blood of Children with Systemic Juvenile Idiopathic Arthritis

Urinary Soluble CD163 Levels Predict IgA Nephropathy Remission Status

Jieduquyuzishen Prescription Attenuates Renal Fibrosis in MRL/lpr Mice via Inhibiting EMT and TGF-β1/Smad2/3 Pathway

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