Adenovirus-mediated over-expression of Septin4 ameliorates hepatic fibrosis in mouse livers infected with Schistosoma japonicum

He, Xue; Bao, Jing; Chen, Jinling; Sun, Xiaolei; Wang, Jianxin; Zhu, Dandan; Song, Ke; Peng, Wenxia; Xu, Tianhua; Duan, Yinong

doi:10.1016/j.parint.2015.07.002

Cited by 12 publications

(8 citation statements)

References 30 publications

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“…In addition, Shen et al ( 18 ) demonstrated that Sept4_i2 sensitized hepatocellular carcinoma cells to serum starvation-induced apoptosis ( 18 ). The results of previous studies also indicated that Sept4_i2 may be involved in Schistosoma japonicum -induced hepatic fibrosis progression, and may regulate apoptosis in HSCs via the PPAR-γ/Akt/Bcl-2 pathway ( 19 – 21 ). Therefore, the present study constructed the eukaryotic recombinant pIRES2-EGFP-ARTS plasmid and determined the effects of ARTS overexpression on LX-2 cells.…”

Section: Discussionmentioning

confidence: 93%

Construction of a recombinant pIRES2-EGFP-ARTS plasmid and its effect on LX-2 cells

Han

Zhu

et al. 2017

Molecular Medicine Reports

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The inhibition of the activation of hepatic stellate cells (HSCs) and the induction of their apoptosis have been investigated as potential strategies to counteract the development and progression of liver fibrosis. Previous research has suggested that apoptosis-related protein in the transforming growth factor-β signaling pathway (ARTS) may serve a significant role in numerous cell types; however, little is known regarding its roles in HSCs. Total RNA was extracted from LX-2 cells, and the human full-length ARTS gene was obtained by reverse transcription-polymerase chain reaction and inserted into the pIRES2-EGFP cloning vector. Subsequently, the recombinant pIRES2-EGFP-ARTS plasmid was transfected into LX-2 cells by FuGENE 6 transfection reagent, and the expression of ARTS was detected by western blotting and fluorescent microscopy. In addition, the effects of pIRES2-EGFP-ARTS on the activation, apoptosis, viability and migration of LX-2 cells were assessed by western blot analysis, TUNEL staining, an MTT assay, and scratch and Transwell assays, respectively. The present results demonstrated that the pIRES2-EGFP-ARTS vector expressing human ARTS was successfully constructed, and the overexpression of ARTS contributed to enhance the apoptosis and inhibit the activation of human LX-2 HSCs. The present findings suggested that ARTS overexpression may have potential as a novel therapeutic strategy to reverse hepatic fibrosis.

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Section: Discussionmentioning

confidence: 93%

Construction of a recombinant pIRES2-EGFP-ARTS plasmid and its effect on LX-2 cells

Han

Zhu

et al. 2017

Molecular Medicine Reports

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“…Septins belong to a class of cytoskeletal proteins with GTPase activity, which can form intracellular filamentous scaffolds. Previous studies have demonstrated that septins are involved in numerous biological processes, such as cell mitosis, polarity determination, vesicle trafficking and apoptosis (21)(22)(23). In addition, our previous study revealed that septin-7, a member of septin family, has an inhibitory effect in melatonin-induced apoptosis (15).…”

Section: Introductionmentioning

confidence: 88%

Relationship between autophagy, apoptosis and endoplasmic reticulum stress induced by melatonin in osteoblasts by septin7 expression

et al. 2020

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Melatonin secreted by the pineal body is associated with the occurrence and development of idiopathic scoliosis. Melatonin has a concentration-dependent dual effect on osteoblast proliferation, in which higher concentrations can inhibit osteoblast proliferation and induce apoptosis; however, the underlying mechanism remains unclear. in the present study, flow cytometry was used to demonstrate that osteoblast cells treated with melatonin exhibited significantly increased early and late stage apoptotic rates as the concentration increased. chromatin condensation in the nucleus and apoptotic body formation could be observed using fluorescent microscopy in osteoblast cells treated with 2 mM melatonin. Western blotting results showed that there was an upregulation in the expression of apoptosis marker proteins [poly (adP-ribose) polymerase 1 (ParP-1)], endoplasmic reticulum stress [erS; c/eBP homologous protein (cHoP) and glucose-regulated protein, 78 kda (GrP78)] and autophagy [microtubule-associated protein 1 light chain 3β (lc3)-i/lc3ii]. ParP-1 expression was not altered when treated with erS inhibitor 4PBa and autophagy inhibitor 3Ma, whereas 4PBa or 3Ma in combination with 2 mM melatonin (or the three together) significantly increased ParP-1 expression. Furthermore, the use of septin7 small interfering RNA confirmed that increased expression of GrP78 and cHoP was related to septin7, and melatoninmediated erS was necessary for septin7 activation. These findings suggest that ERS and autophagy might occur in the early stage of treatment with a high concentration of melatonin, and each might play a protective role in promoting survival; in a later stage, erS and autophagy might interact and contribute to the induction of apoptosis. overall, the results indicated that septin7 may be a target protein of melatonin-induced erS.

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“…Supporting this loss of function data, adenoviral-mediated overexpression of SEPT4 suppresses hepatic fibrosis induced by Schistosoma japonicum infection in mice. 89 Antifibrotic effects of SEPT4 overexpression are associated with inhibition of HSC activity and their increased apoptosis. It is noteworthy that SEPT4 was shown to be a potent regulator of spontaneous and TGF-beinduced apoptosis in different tissues.…”

Section: Tissue Fibrosismentioning

confidence: 99%

Novel Functions of the Septin Cytoskeleton

Ivanov

Naydenov

et al. 2021

The American Journal of Pathology

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Chronic inflammatory diseases cause profound alterations in tissue homeostasis, including unchecked activation of immune and nonimmune cells leading to disease complications such as aberrant tissue repair and fibrosis. Current anti-inflammatory therapies are often insufficient in preventing or reversing these complications. Remodeling of the intracellular cytoskeleton is critical for cell activation in inflamed and fibrotic tissues; however, the cytoskeleton has not been adequately explored as a therapeutic target in inflammation. Septins are GTP-binding proteins that self-assemble into higher order cytoskeletal structures. The septin cytoskeleton exhibits a number of critical cellular functions, including regulation of cell shape and polarity, cytokinesis, cell migration, vesicle trafficking, and receptor signaling. Surprisingly, little is known about the role of the septin cytoskeleton in inflammation. This article reviews emerging evidence implicating different septins in the regulation of hostpathogen interactions, immune cell functions, and tissue fibrosis. Targeting of the septin cytoskeleton as a potential future therapeutic intervention in human inflammatory and fibrotic diseases is also discussed.

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Adenovirus-mediated over-expression of Septin4 ameliorates hepatic fibrosis in mouse livers infected with Schistosoma japonicum

Cited by 12 publications

References 30 publications

Construction of a recombinant pIRES2-EGFP-ARTS plasmid and its effect on LX-2 cells

Construction of a recombinant pIRES2-EGFP-ARTS plasmid and its effect on LX-2 cells

Relationship between autophagy, apoptosis and endoplasmic reticulum stress induced by melatonin in osteoblasts by septin7 expression

Novel Functions of the Septin Cytoskeleton

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