Response Gene to Complement-32 Promotes the Imbalance of Treg/Th17 in Patients with Dilated Cardiomyopathy

Abstract

Background/Aims: The imbalance of Treg/Th17 cells plays important role in the pathogenesis of dilated cardiomyopathy (DCM). Response gene to complement (RGC)-32 is a cell cycle regulator that plays an important role in cell proliferation. We evaluated whether the upregulation of RGC-32 was implicated in the homeostasis of Treg/Th17 cells in DCM. Methods:The levels of plasma RGC-32, IL-17 and TGF-β1, and the frequencies of circulating CD4 + RGC-32 + T cells, Th17 and Treg cells in patients with DCM were determined by Cytokinespecific sandwich ELISA and the flow cytometer (FCM), respectively. Results: A significant elevation of plasma RGC-32 in patients with DCM compared with healthy control (HC) subjects was observed. This upregulation was associated with an increase in frequency of Th17 and a decrease in frequency of Treg cells. To further assessed the role of RGC-32, we investigated the effects of RGC-32 up-or down-regulation on frequencies of Th17 and Treg cells in peripheral blood mononuclear cells (PBMCs) from subjects. Importantly, overexpression of RGC-32 was accompanied by an augmentation of Th17 and a reduction of Treg expression. Conclusion: In summary, our study demonstrated the up-regulation of RGC-32 contributed to the imbalance of Treg/Th17 cells in patients with DCM.

Metabolic reprogramming orchestrates CD4+ T-cell immunological status and restores cardiac dysfunction in autoimmune induced-dilated cardiomyopathy mice

“…Pathological activation of circulating CD4 + T-cells and production of IgG autoantibodies against certain antigens have been identified in DCM patients [9,10,42]. In parallel, an alteration of Treg and Th17 proportions in peripheral blood was identified in these patients [14]. The results obtained in this study, in both patients and a mouse model, agree with the previously described observations, and indicate that CD4 + T-cell activity and functions are altered during DCM development.…”

“…Despite therapeutic progress, further research has shown that some patients remain vulnerable to sudden cardiac death and refractory heart failure, requiring heart transplantation or mechanical circulatory support [2]. A handful of previous studies have reported that immune dysfunction induced by autoimmune disorders plays a vital role in the progression of DCM [3][4][5][6][7][8][9][10][11][12][13][14]. T-cell-mediated immune dysfunction has been linked to a variety of heart diseases, including idiopathic DCM [5][6][7][8].…”

“…T-cell hyperactivation and defective suppressive capacity in Treg cells have been observed in idiopathic DCM patients [12,13]. Moreover, patients with DCM have been found to have an alteration of Treg and Th17 proportions in peripheral blood [14]. Therefore, T-cell dysfunction is involved in the pathogenesis and progression of DCM and may be an underlying therapeutic target for DCM.…”

Response gene to complement 32 expression in macrophages augments paracrine stimulation-mediated colon cancer progression

“…TGF-β1 as a multifunctional cytokine is involved in pathological processes, such as inflammatory response and tumorigenesis [37][38][39] . RGC-32 is a downstream target of TGF-β that mediates epithelialmesenchymal transition and Th17 cell differentiation 40,41 . In this study, our data indicated that RGC-32 expression in macrophages was significantly increased by colon cancer cell-derived TGF-β1.…”

Oncogenic gene RGC‐32 is a direct target of miR‐26b and facilitates tongue squamous cell carcinoma aggressiveness through EMT and PI3K/AKT signalling

“…[8][9][10][11] Extensive researches have shown that RGC-32 induces cell proliferation, differentiation, invasion, migration, epithelial-mesenchymal transition (EMT) occurrence and metabolism. [12][13][14][15][16] A considerable amount of literatures have been published on regulatory effects of RGC-32 in a variety of non-cancerous diseases, concerning vascular diseases, [17][18][19] Alzheimer's Disease, 20 obesity, 21 diabetic retinopathy, 22 autoimmune encephalomyelitis, 23 renal ischemia reperfusion injury, 24 preeclampsia 25 and other non-tumour diseases. In addition to its mediating role in non-cancer, essential roles of it were identified to facilitate the progressions of numerous malignancies, namely ovarian cancer, 26,27 colon cancer, 28,29 prostate cancer, 30 lung cancer, 31,32 breast carcinoma 33 and pancreatic cancer.…”