Gastric cancer (GC) is one of the most common malignancies worldwide. TGF-β1 induces the epithelial-mesenchymal transition (EMT) in GC, mainly through Smad-dependent pathways. Nevertheless, few studies have focused on the activation of non-canonical transduction pathways. TRPC, Ca entry channels, are ubiquitously expressed in various cell types and are involved in many cellular functions. However, their roles in GC are not well elucidated. This study aimed to determine whether TRPC participates in the TGF-β1-induced EMT of GC and to investigate the potential mechanisms. Immunofluorescence staining was performed to examine the distribution and expression of TRPCs and EMT-related proteins in SGC-7901 cells incubated with or without TGF-β1. The expression of TRPC1/3/6 and EMT-related molecules, including E-cadherin, vimentin, and α-SMA, was detected by qRT-PCR and Western blotting. Additionally, the underlying mechanism was determined by treating cells with pharmacological inhibitors and examining the levels of proteins involved in the main signaling cascades using Western blotting. TRPC1/3/6 were expressed at high levels in SGC-7901 cells. Following TGF-β1 stimulation, the expression of vimentin, α-SMA, and TRPC1/3/6 increased and E-cadherin expression decreased, accompanied by activation of the Ras/Raf1/ERK1/2 signaling pathway. Notably, activation of the Ras/Raf1/ERK1/2 signaling cascade was suppressed by SKF96365 and 2-APB. Both TRPC and ERK inhibitors mitigated EMT progression. Based on these results, TRPC1/3/6 inhibition attenuated the TGF-β1-induced EMT in GC by suppressing Ras/Raf1/ERK signal transduction.

The association of polymorphisms in programmed cell death 1 (PDCD1) gene with systemic lupus erythematosus (SLE) risk is inconsistent across different studies. This meta-analysis is aimed to provide reliable evidence to the association of five common PDCD1 polymorphisms (PD1.1, PD1.2, PD1.3, PD1.5 and PD1.6) with SLE risk. A total of 28 studies with 4,344 SLE cases and 5,474 healthy controls were included in this meta-analysis. PD1.3 polymorphism was significantly associated with SLE in the overall population (A vs. G: OR = 1.35, 95% CI = 1.12-1.63; GA vs.GG: OR = 1.41, 95% CI = 1.12-1.76; AA+GA vs. GG: OR = 1.41, 95% CI = 1.13-1.7). In the stratified analyses based on ethnicity, we found a significant association in Caucasians and in Mexicans. In the subgroup analyses by gender, a significant association was found between PD1.3 polymorphism and SLE risk in males. The results also suggested an association between the PD1.6 polymorphism and decreased SLE risk (A vs. G: OR = 0.84, 95% CI = 0.73-0.96). Our meta-analysis revealed that PD1.3 polymorphism may increase the susceptibility to SLE, particularly in Caucasians, while PD1.6 may be a protective factor to SLE.

Background/Aims: IFN-γ was reported to be involved in the development and progression of Immunoglobulin A nephropathy (IgAN), however, few studies have investigated the association between IFN-γ polymorphisms and IgAN. Therefore, we performed a case-control study to assess the association between IFN-γ polymorphisms and the risk of IgAN. Methods: Sequenom MassARRAY was used to genotype two SNPs (rs1861494 and rs2430561) in 351 patients with IgAN and 310 healthy controls. Associations were evaluated as odd ratios (OR) with 95% confidence intervals (CI). Results: No association was found between IFN-γ rs1861494 and IgAN risk or clinical parameters. For rs2430561, the AA genotype was more common in patients with IgAN, compared with controls (AT vs. AA: OR = 0.57, P = 0.035). IFN-γ-rs2430561 T allele may be a protective factor for IgAN susceptibility (T vs. A: OR = 0.59, P = 0.04). Subgroup analysis based on clinical features revealed no significant association between rs2430561 polymorphism and clinical data such as gender, 24-h urine protein, blood pressure, Oxford classifcation and estimated glomerular fltration rate. IgAN patients had a higher IFN-γ serum level than healthy controls and patients with rs1861494 AA genotype had a higher IFN-γ serum level compared with those with AG/GG genotypes. Conclusions: IFN-γ polymorphisms may be involved in the development and progression of IgAN.

Monocyte chemoattractant protein-1 (MCP-1) and its receptor CCR2 stimulate inflammation response by activating and recruiting monocytes/macrophages. MCP-1 and CCR2 polymorphisms were reported to be associated with various diseases. To explore the relationship between MCP-1 and CCR2 polymorphisms and IgA nephropathy (IgAN), we conducted this case-control study by enrolling 351 IgAN patients and 310 health controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to evaluate potential associations of MCP-1 and CCR2 polymorphisms with susceptibility and clinical parameters of IgAN. No statistical differences between IgAN group and the control group in the MCP-1 -2518 and CCR2 +190 genotypic groups were observed (P > 0.05). Individuals with MCP-1 -2518 GG genotypes had a higher blood pressure (GG vs. AA+AG: OR = 1.79, 95% CI = 1.07-2.99, P = 0.026) and Lee's grade (GG vs. AA+AG: OR = 2.05, 95% CI = 1.19-3.54, P = 0.009; GG vs. AA: OR = 2.24, 95% CI = 1.19-4.20, P = 0.01), compared with patients with AA/AG genotypes. A significant association between CCR2 +190 polymorphism and Lee's grades was observed (GA+AA vs. GG: OR = 2.66, 95% CI = 1.63-4.35, P < 0.001; GA vs. AA+GG: OR = 2.27, 95% CI = 1.39-3.70, P = 0.001). Our results indicated that MCP-1 and CCR2 polymorphisms may influence the progression of IgAN, but not increase/decrease its susceptibility.

Background/Aims: IgA nephropathy (IgAN) is a common form of primary glomerulonephritis worldwide. Previous studies indicated that IL-10 single nucleotide polymorphisms (SNP) play an important role in IgAN pathogenesis, but the results were controversy. This study aimed to investigate the association between IL-10 SNPs (rs1800872, rs1800871, and rs1800896) with IgAN in a Chinese Han population. Methods: We conducted a case–control study that included 351 patients with IgAN and 310 age-, gender- and ethnicity-matched healthy controls. Three promoter SNPs (rs1800872, rs1800871, and rs1800896) of IL-10 were genotyped by Sequenom MassARRAY. Odds ratios (ORs) with 95% confidence intervals (CI) were used to assess the relationship with IgAN. Results: We found that the rs1800896 did not correlate with IgAN risk, whereas rs1800872 and rs1800871 were significantly associated with increased IgAN risk in all genetic models. The haplotype analysis indicated that the CCA haplotype was associated with increased IgAN risk (OR = 1.36; 95% CI = 1.05–1.75). Moreover, there were no associations between these SNPs and blood pressure or gender, whereas the rs1800896 variant was correlated with higher 24-hour urine protein in patients with IgAN. Conclusion: Taken together, these results suggest that IL-10 is a susceptibility gene in patients with IgAN.

Toll-like receptors (TLRs) are a family of transmembrane receptors, and play a vital role in recognizing invading pathogens and activating innate immunity. Previous studies indicated that TLR1 single nucleotide polymorphisms (SNPs) might be associated with the risk of IgA nephropathy (IgAN). This study aims to investigate the relationship between TLR1 SNPs (rs4833095 and rs5743557) and IgAN in a Chinese Han population. This case-control study included 351 patients with IgAN and 310 healthy controls. Two SNPs (rs4833095 and rs5743557) of TLR1 were genotyped by Sequenom MassARRAY. Odds ratios (OR) with 95% confidence intervals (CI) were used to assess the relationship with IgAN. We found that both allele and genotype frequencies of rs5743557 were not associated with IgAN risk. Rs4833095 increased IgAN risk compared with controls in the allele, dominant and log-additive models (P = 0.04, 0.04 and 0.03, respectively). Further haplotype analysis revealed that the Trs4833095Trs5743557 haplotype may be a risk factor for IgAN (OR = 1.28; 95% CI = 1.01–1.63; P = 0.046). Furthermore, rs4833095 was associated with Lee's grades (OR = 1.75; 95% CI = 1.03–2.96; P = 0.04). However, there was no significant association between the genotype distributions of rs5743557 and clinical parameters of IgAN such as gender, 24 hour urine protein, blood pressure, and Lee's grades. Taken together, these findings suggest that the TLR1 rs4833095 polymorphism may play a role in the development and progression of IgAN.

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Dipeptidyl peptidase 8 (DPP8) and 9 (DPP9) are widely expressed in mammals including humans, mainly locate in the cytoplasm. The DPP8 and DPP9 (DPP8/9) belong to serine proteolytic enzymes, they can recognize and cleave N-terminal dipeptides of specific substrates if proline is at the penultimate position. Because the localization of DPP8/9 is different from that of DPP4 and the substrates for DPP8/9 are not yet completely clear, their physiological and pathological roles are still being further explored. In this article, we will review the recent research advances focusing on the expression, regulation, and functions of DPP8/9 in physiology and pathology status. Emerging research results have shown that DPP8/9 is involved in various biological processes such as cell behavior, energy metabolism, and immune regulation, which plays an essential role in maintaining normal development and physiological functions of the body. DPP8/9 is also involved in pathological processes such as tumorigenesis, inflammation, and organ fibrosis. In recent years, related research on immune cell pyroptosis has made DPP8/9 a new potential target for the treatment of hematological diseases. In addition, DPP8/9 inhibitors also have great potential in the treatment of tumors and chronic kidney disease.