Ginsenoside‐Rg1 attenuates sepsis‐induced cardiac dysfunction by modulating mitochondrial damage via the P2X7 receptor‐mediated Akt/GSK‐3β signaling pathway

Abstract Background Metastasis and invasion are crucial in determining the mortality of cervical carcinoma (CC) patients. The epithelial–mesenchymal transition (EMT) is now a universal explanation for the mechanisms of tumor metastasis. Α-chimeric protein (α-chimaerin, CHN1) plays an important role in the regulation of signal transduction and development. However, the molecular regulatory relationships between CHN1 and CC progression in relation to EMT have not yet been identified. Methods The expression of CHN1 in CC tissues, adjacent tissues, and lymph node metastases from CC patients was detected by immunohistochemistry. Upregulation and knockdown of CHN1 were achieved by transfection of CC cells. The effect of CHN1 on cell proliferation was determined by CCK-8 and plate clone formation assays. Changes in migration and invasion capabilities were evaluated using scratch migration and transwell invasion assays. The effect of CHN1 overexpression and interference on xenograft tumor growth was determined by tumor weight and pathological analyses. The expression of EMT-related mRNAs was measured by qRT-PCR in transfected CC cells. EMT-related proteins and Akt/GSK-3β/Snail signaling pathway-related proteins were also evaluated by western blotting. Results CHN1 was overexpressed in CC tissues and was associated with lymph node metastasis and low survival in CC patients. Overexpression of CHN1 promoted cell proliferation, migration, and invasion in CC cells. In contrast, silencing of CHN1 inhibited these phenomena. Overexpression of CHN1 promoted tumor formation in an in vivo xenograft tumor mouse model, with increased tumor volumes and weights. In addition, CHN1 induced the expression of EMT-related transcription factors, accompanied by the decreased expression of epithelial markers and increased expression of mesenchymal markers. The Akt/GSK-3β/Snail signaling pathway was activated by overexpression of CHN1 in vitro, and activation of this pathway was inhibited by the signaling pathway inhibitor LY294002. Conclusion These results suggest that CHN1 promotes the development and progression of cervical carcinoma via the Akt/GSK-3β/Snail pathway by inducing EMT.

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Tryptophan 2,3-dioxygenase 2 controls M2 macrophages polarization to promote esophageal squamous cell carcinoma progression via AKT/GSK-3β/IL-8 signaling pathway

Acta Pharmaceutica Sinica B ◽

10.1016/j.apsb.2021.03.009 ◽

2021 ◽

Author(s):

Yumiao Zhao ◽

Jiaxin Sun ◽

Yin Li ◽

Xiuman Zhou ◽

Wenjie Zhai ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Esophageal Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Signaling Pathway ◽

Squamous Cell ◽

M2 Macrophages ◽

Macrophages Polarization ◽

Gsk 3Β

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Cadmium inhibits neural stem/progenitor cells proliferation via MitoROS‐dependent AKT/GSK‐3β/β‐catenin signaling pathway

Journal of Applied Toxicology ◽

10.1002/jat.4179 ◽

2021 ◽

Author(s):

Huan Luo ◽

Bo Song ◽

Guiya Xiong ◽

Bing Zhang ◽

Zhenzi Zuo ◽

...

Keyword(s):

Progenitor Cells ◽

Signaling Pathway ◽

Neural Stem Progenitor Cells ◽

Gsk 3Β

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Pinocembrin inhibited cardiomyocyte pyroptosis against doxorubicin-induced cardiac dysfunction via regulating Nrf2/Sirt3 signaling pathway

International Immunopharmacology ◽

10.1016/j.intimp.2021.107533 ◽

2021 ◽

Vol 95 ◽

pp. 107533

Author(s):

Jiwei Gu ◽

Hui Huang ◽

Chunlian Liu ◽

Bo Jiang ◽

Mingliang Li ◽

...

Keyword(s):

Signaling Pathway ◽

Cardiac Dysfunction

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RTEF-1 Inhibits Vascular Smooth Muscle Cell Calcification through Regulating Wnt/β-Catenin Signaling Pathway

Calcified Tissue International ◽

10.1007/s00223-021-00833-4 ◽

2021 ◽

Author(s):

Jingjing Cong ◽

Bei Cheng ◽

Jinyu Liu ◽

Ping He

Keyword(s):

Smooth Muscle ◽

Vascular Smooth Muscle ◽

Osteogenic Differentiation ◽

Signaling Pathway ◽

Glycogen Synthase ◽

Critical Role ◽

Transcriptional Enhancer ◽

Alizarin Red ◽

Gsk 3Β ◽

Enhancer Factor

AbstractVascular calcification (VC) is highly prevailing in cardiovascular disease, diabetes mellitus, and chronic kidney disease and, when present, is associated with cardiovascular events and mortality. The osteogenic differentiation of vascular smooth muscle cells (VSMCs) is regarded as the foundation for mediating VC. Related transcriptional enhancer factor (RTEF-1), also named as transcriptional enhanced associate domain (TEAD) 4 or transcriptional enhancer factor-3 (TEF-3), is a nuclear transcriptional factor with a potent effect on cardiovascular diseases, apart from its oncogenic role in the canonical Hippo pathway. However, the role and mechanism of RTEF-1 in VC, particularly in calcification of VSMCs, are poorly understood. Our results showed that RTEF-1 was reduced in calcified VSMCs. RTEF-1 significantly ameliorated β-glycerophosphate (β-GP)-induced VSMCs calcification, as detected by alizarin red staining and calcium content assay. Also, RTEF-1 reduced alkaline phosphatase (ALP) activity and decreased expressions of osteoblast markers such as Osteocalcin and Runt-related transcription factor-2 (Runx2), but increased expression of contractile protein, including SM α-actin (α-SMA). Additionally, RTEF-1 inhibited β-GP-activated Wnt/β-catenin pathway which plays a critical role in calcification and osteogenic differentiation of VSMCs. Specifically, RTEF-1 reduced the levels of Wnt3a, p-β-catenin (Ser675), glycogen synthase kinase-3β (GSK-3β), and p-GSK-3β (Ser9), but increased the levels of p-β-catenin (Ser33/37). Also, RTEF-1 increased the ratio of p-β-catenin (Ser33/37) to β-catenin proteins and decreased the ratio of p-GSK-3β (Ser9) to GSK-3β protein. LiCl, a Wnt/β-catenin signaling activator, was observed to reverse the protective effect of RTEF-1 overexpression on VSMCs calcification induced by β-GP. Accordingly, Dickkopf-1 (Dkk1), a Wnt antagonist, attenuated the role of RTEF-1 deficiency in β-GP-induced VSMCs calcification. Taken together, we concluded that RTEF-1 ameliorated β-GP-induced calcification and osteoblastic differentiation of VSMCs by inhibiting Wnt/β-catenin signaling pathway.

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