TMEM100 mediates inflammatory cytokines secretion in hepatic stellate cells and its mechanism research

Pan, Linxin; Li, Liang-yun; Zhou, Hong; Cheng, Shu-qi; Liu, Yumin; Lian, Panpan; Li, Li; Wang, Lele; Rong, Shan-Jie; Shen, Chuan-pu; Li, Jun; Xu, Tao

doi:10.1016/j.toxlet.2018.12.010

Cited by 14 publications

(23 citation statements)

References 41 publications

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“…Previous studies have shown that inflammation and oxidative stress promote the activation of MAPK signaling pathway. MAPK signaling pathway promotes the proliferation and activation of HSC ( Pan et al, 2019 ) ( Peng et al, 2013 ), and can also stimulate the production of collagen ( Cao et al, 2006 ). Accordingly, inhibition of the progression of hepatic fibrosis by suppressing HSCs proliferation and activation and production of collagen via MAPK signaling pathway.…”

Section: Discussionmentioning

confidence: 99%

Uncovering the Pharmacological Mechanisms of Gexia-Zhuyu Formula (GXZY) in Treating Liver Cirrhosis by an Integrative Pharmacology Strategy

et al. 2022

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Liver cirrhosis (LC) is a fibrotic lesion of liver tissue caused by the repeated progression of chronic hepatitis. The traditional Chinese medicine Gexia-Zhuyu formula (GXZY) has a therapeutic effect on LC. However, its pharmacological mechanisms on LC remain elucidated. Here, we used the network pharmacology approach to explore the action mechanisms of GXZY on LC. The compounds of GXZY were from the traditional Chinese medicine systems pharmacology (TCMSP) database, and their potential targets were from SwissTargetPrediction and STITCH databases. The disease targets of LC came from GeneCards, DisGeNET, NCBI gene, and OMIM databases. Then we constructed the protein-protein interaction (PPI) network to obtain the key target genes. And the gene ontology (GO), pathway enrichment, and expression analysis of the key genes were also performed. Subsequently, the potential action mechanisms of GXZY on LC predicted by the network pharmacology analyses were experimentally validated in LC rats and LX2 cells. A total of 150 components in GXZY were obtained, among which 111 were chosen as key compounds. The PPI network included 525 targets, and the key targets were obtained by network topological parameters analysis, whereas the predicted key genes of GXZY on LC were AR, JUN, MYC, CASP3, MMP9, GAPDH, and RELA. Furthermore, these key genes were related to pathways in cancer, hepatitis B, TNF signaling pathway, and MAPK signaling pathway. The in vitro and in vivo experiments validated that GXZY inhibited the process of LC mainly via the regulation of cells proliferation and migration through reducing the expression of MMP9. In conclusion, through the combination of network pharmacology and experimental verification, this study offered more insight molecular mechanisms of GXZY on LC.

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Section: Discussionmentioning

confidence: 99%

Uncovering the Pharmacological Mechanisms of Gexia-Zhuyu Formula (GXZY) in Treating Liver Cirrhosis by an Integrative Pharmacology Strategy

et al. 2022

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“…In hepatic stellate cells, TMEM100 overexpression leads to down-regulation of IL-1β and IL-6 secretion. 43 TMEM100 may serve as a tumor suppressor in non‑small cell lung cancer and promote autophagy and apoptosis; 44 however, the role of TMEM100 in pyroptosis requires clarification. FAM3B, a member of the Family with sequence similarity 3 group of proteins, has different expression levels in various tumor types.…”

Section: Discussionmentioning

confidence: 99%

A Novel Pyroptosis-Related Prognostic Signature for Cervical Squamous Cell Carcinoma

T¹,

Wei²,

Long³

et al. 2022

IJGM

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Purpose Pyroptosis has vital roles in tumorigenesis and cancer development; however, its relationship with cervical squamous cell cancer (CSCC) remains unexplored. In this study, we aimed to develop a CSCC prediction signature related to pyroptosis. Patients and Methods Consensus clustering analysis was conducted to detect pyroptosis-related subclusters for CSCC. Next, differentially expressed genes (DEGs) between subclusters were identified. Univariate, least absolute shrinkage and selection operator, and stepwise multivariate Cox regression analyses were applied to establish a prognostic model and a nomogram drawn. Additionally, functional enrichment analysis, tumor mutation burden, and immune characteristics associated with this signature were investigated. Results We constructed a seven-gene signature that functions as an independent predictor of prognosis in CSCC using data from The Cancer Genome Atlas. Patients with CSCC were divided into two groups based on median risk score, and patients in the low-risk group had significantly longer survival time than those in the high-risk group. Our findings were validated using Gene Expression Omnibus cohort data. We also established a nomogram, to expand the clinical applicability of our findings. The seven gene signature was associated with various molecular pathways, tumor mutation status, and immune microenvironment. Conclusion The pyroptosis-related risk signature consisting of seven genes developed here represents a potential robust biomarker for predicting prognosis and immunotherapy response in patients with CSCC.

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“…For instance, BMP-activin receptor-like kinase 1 (ALK1)-transmembrane protein 100 (TMEM100) signaling plays a pivotal role in inflammation, cell apoptosis, and proliferation and metastasis of tumors. 40 An increasing number of studies have demonstrated the functions of BMPs in liver fibrosis. However, BMPs play different roles in liver fibrosis, selectively targeting them poses a promising approach for liver fibrosis treatment.…”

Section: Discussionmentioning

confidence: 99%

The role of bone morphogenetic proteins in liver fibrosis

Ming¹,

Zhang²

2021

GHOA

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Liver fibrosis is featured by excessive accumulation of extracellular matrix (ECM) proteins in the injury liver of diseases, including alcoholic liver disease (ALD), non-alcoholic fatty liver disease (NAFLD) and steatohepatitis (NASH), cirrhosis, and hepatocellular cancer (HCC). However, there is no current therapy for preventing and reversing liver fibrosis. Transforming growth factor-β1 (TGF-β1) is a key profibrotic gene that drives activation of hepatic stellate cells (HSCs) and their transdifferentiation to myofibroblasts producing ECM proteins. Bone morphogenetic proteins (BMPs) belonging to TGF-β big family play important roles in tissue morphogenesis and homeostasis in the bone, cartilage, muscle, kidney, and blood vessels. Accumulating evidence indicates that BMPs are involved in the development and progression of liver fibrosis and liver regeneration. In this review, we summarize the recent findings of the dual roles of BMPs in liver fibrosis. Strategies have been developed to target these molecules to treat liver fibrosis. However, the efficacy is under expectation. Therefore, better understanding of the underlying mechanisms of BMPs in the progression of liver disease is critically important for improving their therapeutic effect.

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TMEM100 mediates inflammatory cytokines secretion in hepatic stellate cells and its mechanism research

Cited by 14 publications

References 41 publications

Uncovering the Pharmacological Mechanisms of Gexia-Zhuyu Formula (GXZY) in Treating Liver Cirrhosis by an Integrative Pharmacology Strategy

Uncovering the Pharmacological Mechanisms of Gexia-Zhuyu Formula (GXZY) in Treating Liver Cirrhosis by an Integrative Pharmacology Strategy

A Novel Pyroptosis-Related Prognostic Signature for Cervical Squamous Cell Carcinoma

The role of bone morphogenetic proteins in liver fibrosis

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