ALK7 Gene Polymorphism is Associated with Metabolic Syndrome Risk and Cardiovascular Remodeling

Zhang, Wenchao; Wang, Hui; Zhang, Wei; Lv, Ruijuan; Wang, Wenwen; Shang, Yuanyuan; Zhang, Yun; Zhong, Ming; Chen, Yuguo; Tang, Mengxiong

doi:10.5935/abc.20130129

Cited by 2 publications

(2 citation statements)

References 24 publications

(33 reference statements)

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“…The signaling pathway mediated by ALK7 plays an important role in cell apoptosis, proliferation, and tissue development, and is involved in neuromuscular diseases, endocrine disorders, obesity, tumors, and other diseases. ALK7-related signaling pathways have some important regulatory effects on the body [ 9 – 11 ]. High level of ALK7 is observed in breast cancer tissues and ALK7 overexpression inhibited cell growth and adhesion [ 12 ].…”

Section: Introductionmentioning

confidence: 99%

ALK7 Knockdown Plays a Protective Role on HG-Stimulated MCs through Activation of the Nrf2/HO-1 Pathway

Gao

et al. 2022

Disease Markers

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Objective. Activin receptor-like kinase 7 (ALK7) is a member of the ALK family that has a key role in diabetes. However, the role of ALK7 in diabetic nephropathy (DN) remains unclear. Methods. Herein, we evaluated the effects of ALK7 on mesangial cells (MCs). MCs were transfected with si-ALK7 or pcDNA3.0-ALK7, and then stimulated with 40 mM glucose for 24 h. Cell proliferation was detected by MTT assay. Relative ROS level was detected using DCFH-DA staining. The contents of inflammatory cytokines were determined by ELISA. Western blot analysis was used to determine the expression levels of FN, Col IV, Nrf2, and HO-1 in MCs. Results. Our results showed that ALK7 expression was induced by HG in MCs. Knockdown of ALK7 inhibited HG-induced cell proliferation. The HG-induced ROS was mitigated by si-ALK7 with decreased ROS level and NOX activity. In addition, ALK7 knockdown exhibited anti-inflammatory activity in HG-stimulated MCs. Moreover, ALK7 knockdown attenuated fibronectin (FN) and collagen IV (Col IV) expression in MCs. Knockdown of ALK7 enhanced Nrf2/HO-1 pathway in MCs. Inhibition of Nrf2 reversed the protective effects of ALK7 knockdown on HG-stimulated MCs. Conclusion. ALK7 knockdown exerted protective effects on HG-stimulated MCs through activation of the Nrf2/HO-1 pathway. Thus, targeting ALK7 might be a therapeutic approach for the treatment of DN.

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Section: Introductionmentioning

confidence: 99%

ALK7 Knockdown Plays a Protective Role on HG-Stimulated MCs through Activation of the Nrf2/HO-1 Pathway

Gao

et al. 2022

Disease Markers

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“…It has been reported that deficiency of TLR4 affects doxorubicin-induced cardiomyopathy in mice [14]. Aberrant expression or genetic polymorphisms is recognized as a risk factor for metabolic syndrome and is associated with cardiovascular remodeling [15]. Kiechl et al have reported that TLR4 polymorphisms are associated with heart disease, such as atherogenesis [16].…”

Section: Introductionmentioning

confidence: 99%

Prognostic predictive value of TLR4 polymorphisms in Han Chinese population with hypertrophic cardiomyopathy

Han

2018

The Kaohsiung J of Med Scie

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Hypertrophic cardiomyopathy (HCM) is the most common genetic cardiac disease and is an important cause of sudden death in patients of all ages. The aim of this study was to find out whether Toll‐like receptor‐4 (TLR4) polymorphism is associated with HCM. To explore the association between TLR4 gene polymorphisms and HCM, 486 HCM patients and 214 healthy controls were enrolled in a case–control study of Chinese Han population. Two single nucleotide polymorphisms (SNPs) in the promoter region of TLR4 gene, −728G > C (rs11536865) and −2081G > A (rs10983755), were genotyped by PCR restriction fragment length polymorphism (PCR‐RFLP). The associations between TLR4 SNPs and overall survival (OS) of HCM patients were analyzed by the Kaplan–Meier estimation method and Cox proportional hazards regression analysis. Serum TLR4 level was determined by ELISA. Our results showed that the C allelic frequency of −728G > C and A allelic frequency of −2081G > A were higher in HCM patients than those in controls (P < 0.001). The ratios of genotype frequencies for both SNPs were associated with HCM susceptibility under three genetic models (P < 0.01). Two SNPs were also associated with the OS in HCM patients (P < 0.001). The CC genotype of −728G > C and AA genotype of −2081G > A were associated with poor prognosis of HCM (P < 0.001). Moreover, HCM patients had a higher serum TLR4 level compared with the controls (242.6 pg/ml versus 135.7 pg/ml, P = 0.027). In addition, significant associations were observed between CC genotype of −728G > C or AA genotype of −2081G > A and plasma TLR4 level (P < 0.01). The results of this study indicated that TLR4 polymorphisms may be a genetic susceptibility factor for HCM in the Han Chinese population.

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ALK7 Gene Polymorphism is Associated with Metabolic Syndrome Risk and Cardiovascular Remodeling

Cited by 2 publications

References 24 publications

ALK7 Knockdown Plays a Protective Role on HG-Stimulated MCs through Activation of the Nrf2/HO-1 Pathway

ALK7 Knockdown Plays a Protective Role on HG-Stimulated MCs through Activation of the Nrf2/HO-1 Pathway

Prognostic predictive value of TLR4 polymorphisms in Han Chinese population with hypertrophic cardiomyopathy

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