TGF-β1 mimics the effect of IL-4 on the glycosylation of IgA1 by downregulating core 1 β1, 3-galactosyltransferase and Cosmc

Xiao, Jun; Wang, Manting; Xiong, Dawei; Wang, Ying; Li, Qiuyue; Zhou, Jing; Chen, Qinkai

doi:10.3892/mmr.2016.6084

Cited by 13 publications

(12 citation statements)

References 42 publications

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“…Cosmc was a specific molecular modulator in endoplasmic reticulum for the T‐synthase, one Golgi ß1, 3‐galactosyltransferase which synthesizes the Galß1, 3GalNAcα‐Ser/Thr, in the glycoproteins . The Cosmc dysfunction may lead to the inactive T‐synthase formation and Tn antigen consequent expression, which was correlated with the Tn syndrome and IgAN . It was reported that defect of IgA1 dysglycosylation caused by the Cosmc gene expression was one of crucial pathogenic causes of IgAN .…”

Section: Discussionmentioning

confidence: 99%

MiR‐320 promotes B cell proliferation and the production of aberrant glycosylated IgA1 in IgA nephropathy

Shi

Zhao

2018

J of Cellular Biochemistry

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IgA nephropathy (IgAN) is one of the most common primary glomerulonephritis. However, the etiology of this disease is complex and the pathogenesis of IgAN is still unknown. MicroRNAs (miRNAs) play important roles in a lot of pathological and physiological processes. In this study, we showed that the expression of miR-320 was significantly upregulated in renal tissues and urinary of IgAN patients. Moreover, the intra-renal expression level of miR-320 had significant correlation with miR-320 expression in the urinary of IgAN patients. Overexpression of miR-320 increased B cell proliferation and promoted cyclin D1 expression. Furthermore, we identified that PTEN was direct target gene of miR-320 in the B cell. Ectopic expression of miR-320 suppressed PTEN expression. Overexpression of miR-320 decreased Cosmc expression in the B cell. In addition, we demonstrated that Cosmc expression was significantly downregulated in the renal tissues and urinary of IgAN patients. The intra-renal expression level of Cosmc had significant correlation with Cosmc expression of urinary in IgAN patients. We proved that the expression level of Cosmc was negatively correlated with the expression of miR-320 in the renal tissues of IgAN patients. Overexpression of miR-320 promoted the B cell proliferation through suppressing PTEN expression. Taken together, these data suggested that miR-320 acted an important role in the development of IgAN.

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Section: Discussionmentioning

confidence: 99%

MiR‐320 promotes B cell proliferation and the production of aberrant glycosylated IgA1 in IgA nephropathy

Shi

Zhao

2018

J of Cellular Biochemistry

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“…What is more important, TGF-β significantly decreases the mRNA levels of C1GALT1 and C1GALT1C1 , and thus contributes to the higher production of Gd-IgA1 (Fig. 1) [57]. However, TGF-β does not affect sialylation of IgA1 [57].…”

Section: Elevated Synthesis Of Gd-iga1—the Role Of Th2 Th17 and Tfh-mentioning

confidence: 99%

T cells in IgA nephropathy: role in pathogenesis, clinical significance and potential therapeutic target

et al. 2018

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Background Immunoglobulin A nephropathy (IgAN), the most frequent cause of primary glomerulonephritis worldwide, is an autoimmune disease with complex pathogenesis. In this review, we focus on T cells and summarize knowledge about their involvement in pathophysiology and treatment of IgAN Methods We reviewed the literature for (1) alterations of T cell subpopulations in IgAN, (2) experimental and clinical proofs for T cells’ participation in IgAN pathogenesis, (3) clinical correlations with T cell-associated alterations, and (4) influence of drugs used in IgAN therapy on T cell subpopulations. Results We found that IgAN is characterized by higher proportions of circulatory Th2, Tfh, Th17, Th22 and γδ T cells, but lower Th1 and Treg cells. We discuss genetic and epigenetic makeup that may contribute to this immunological phenotype. We found that Th2, Th17 and Tfh-type interleukins contribute to elevated synthesis of galactose-deficient IgA1 (Gd-IgA1) and that the production of anti-Gd-IgA1 autoantibodies may be stimulated by Tfh cells. We described the roles of Th2, Th17, Th22 and Treg cells in the renal injury and summarized correlations between T cell-associated alterations and clinical features of IgAN (proteinuria, reduced GFR, hematuria). We detailed the impact of immunosuppressive drugs on T cell subpopulations and found that the majority of drugs have nonoptimal influence on T cells in IgAN patients. Conclusions T cells play an important role in IgAN pathogenesis and are correlated with its clinical severity. Clinical trials with the drugs targeting the reported alterations of the T-cell compartment are highly desirable.

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“…On the other hand, previous studies have suggested that in severe renal insufficiency there is an increase in Th2 cytokines and IL-4 in patients with IgAN compared with that in the controls (27,53). In addition, Th2 cytokines induce poor glycosylation of IgA and involvement of these cytokines in Th2-dependent modifications of the sugar chain in the gastrointestinal mucosa and tonsils have also been demonstrated (53)(54)(55). Furthermore, the cytokine, IL-4, secreted by Th2 may play an important role in controlling glycosylation of the IgA1 HR (45) and renal fibrosis (46).…”

Section: Th1/th2 Lymphocytesmentioning

confidence: 98%

T lymphocytes in IgA nephropathy (Review)

Tang

et al. 2020

Exp Ther Med

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Immunoglobulin A nephropathy (IgAN), the most common primary glomerulonephritis worldwide, is the main cause of end-stage renal disease. IgAN is characterized by the accumulation of immune complexes in the circulation, which contain abnormal levels of IgA. IgAN primarily results from galactose-deficient IgA1 (Gd-IgA1) and Gd-IgA1 deposition in the renal mesangium, causing local proliferation and matrix expansion. Gd-IgA1 has been confirmed as one of the key effectors in the pathogenesis of IgAN, but the origin of Gd-IgA1 is not clear. Recent studies have shown that Gd-IgA1 deposition could be the result of mucosally primed plasma cells and is associated with T cell dysregulation. T cells contribute to the IgA response and play an important role in the development of IgAN. In the present review, the latest discoveries regarding the role of T lymphocytes in the pathogenesis of IgAN have been summarized. Understanding these advances will allow novel therapeutic strategies for the treatment of IgAN.

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TGF-β1 mimics the effect of IL-4 on the glycosylation of IgA1 by downregulating core 1 β1, 3-galactosyltransferase and Cosmc

Cited by 13 publications

References 42 publications

MiR‐320 promotes B cell proliferation and the production of aberrant glycosylated IgA1 in IgA nephropathy

MiR‐320 promotes B cell proliferation and the production of aberrant glycosylated IgA1 in IgA nephropathy

T cells in IgA nephropathy: role in pathogenesis, clinical significance and potential therapeutic target

T lymphocytes in IgA nephropathy (Review)

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