The Role of Renal Macrophage, AIM, and TGF-β1 Expression in Renal Fibrosis Progression in IgAN Patients

Yang, Min; Liu, Jia Wei; Zhang, Yu Ting; Wu, Gang

doi:10.3389/fimmu.2021.646650

Cited by 23 publications

(24 citation statements)

References 39 publications

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“…Moreover, gene ontology functional enrichment among the 640 genes revealed that they were mainly enriched in terms of “transforming growth factor beta”, “apoptotic process”, “NF-kappa B signaling” and “toll-like receptor signaling pathway”, “kinase regulator activity” and “cell adhesion” (Fig. 8G ), which were previously demonstrated to related to renal fibrosis or ECM deposition [ 20 – 22 ]. KYOTO ENCYCLOPEDIA OF GENES AND GENOMES pathway enrichment among these genes showed that they were mainly enriched in terms of “TNF signaling pathway”, “Hepatitis” and “virus infection” (Fig.…”

Section: Resultsmentioning

confidence: 93%

The mmu_circRNA_37492/hsa_circ_0012138 function as potential ceRNA to attenuate obstructive renal fibrosis

Lee

et al. 2022

Cell Death Dis

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Circular RNAs (circRNAs) are involved in the pathogenesis of certain renal diseases, however, the function and mechanism of them in renal fibrosis remains largely unknown. In the present study, RNA expression data in unilateral ureteral obstruction (UUO) kidneys was obtained from our previous circRNA Microarray and public Gene Expression Omnibus datasets to construct a ceRNA network. The effects of target circRNA as long as the homologous human circRNA on renal fibrosis was examined in vitro and in vivo. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis was further performed among genes regulated by the human circRNA. We found that circRNA_37492, showing well connection degree in the ceRNA network, was abundant expression and high sequence conservation. We observed that the expression of circRNA_37492 was induced by the TGF-β1 or UUO in BUMPT cells and C57BL/6 mice, respectively. In vitro, cytoplasmic circRNA_37492 inhibited type I, III collagen and fibronectin deposition by sponging miR-7682-3p and then upregulated its downstream target Fgb. In vivo, overexpression of circRNA_37492 attenuated fibrotic lesions in the kidneys of UUO mice via targeting miR-7682-3p/Fgb axis. Furthermore, hsa_circ_0012138, homologous with circRNA_37492, may potentially target miR-651-5p/FGB axis in human renal fibrosis. Not only that, GO and KEGG enrichment revealed that hsa_circ_0012138-regulated genes were previously demonstrated to related to the fibrosis. In conclusion, we for the first time demonstrated that circRNA_37492 attenuated renal fibrosis via targeting miR-7682-3p/Fgb axis, and the homologous hsa_circRNA_0012138 was speculated as a possible ceRNA to regulate multiple gene expressions and involve in human renal fibrosis, suggesting that circRNA_37492/hsa_circ_0012138 may serve as potent therapy target for obstructive renal fibrosis disease.

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Section: Resultsmentioning

confidence: 93%

The mmu_circRNA_37492/hsa_circ_0012138 function as potential ceRNA to attenuate obstructive renal fibrosis

Lee

et al. 2022

Cell Death Dis

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“…In the process of EMT, epithelial cells adapt to the stimulation of the immune microenvironment, thereby changing the plasticity phenotype. Macrophages in the immune microenvironment are considered to be the main part of driving kidney inflammation and fibrosis, because they synthesize and secrete a variety of molecules that promote or participate in the process of kidney fibrosis, such as growth factors, enzymes, and matrix proteins [ 37 , 38 ]. Among them, TGF- β secreted by macrophages is considered to be one of the main factors that promote fibrosis [ 39 ].…”

Section: Discussionmentioning

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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“…CD163 + macrophages are considered to be M2c macrophages with anti-inflammatory and pro-fibrotic functions ( 10 ). Indeed, previous studies on IgAN showed that CD163 + macrophage subsets correlated with degree of interstitial fibrosis ( 21 ), and that CD163 + macrophages play a more important role in progression of IgAN fibrosis than other kinds of macrophages ( 8 ). 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.…”

Section: Discussionmentioning

confidence: 99%

“…Wound-healing macrophages (M2a), M2b and regulatory macrophages (M2c) ( 7 ). Macrophages infiltration in IgAN kidneys are predominantly composed of CD163 + M2c macrophages ( 8 ).…”

Section: Introductionmentioning

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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The Role of Renal Macrophage, AIM, and TGF-β1 Expression in Renal Fibrosis Progression in IgAN Patients

Cited by 23 publications

References 39 publications

The mmu_circRNA_37492/hsa_circ_0012138 function as potential ceRNA to attenuate obstructive renal fibrosis

The mmu_circRNA_37492/hsa_circ_0012138 function as potential ceRNA to attenuate obstructive renal fibrosis

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

Urinary Soluble CD163 Levels Predict IgA Nephropathy Remission Status

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