Astragaloside IV protects cardiomyocytes against hypoxia injury via HIF-1α and the JAK2/STAT3 pathway

Li, Bei; Yu, Junjian; Li, Peipei; Zeng, Taohui; Zeng, Xiangwu

doi:10.21037/atm-21-4080

Cited by 9 publications

(5 citation statements)

References 59 publications

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“…Under hypoxia, HIF‐1α is stabilized and translocated to the nucleus, where it forms a complex with HIF‐1β and thus initiates the transcription of target genes. [ 15,16 ] The expression level of HIF‐1α in human aortic dissection tissues is prominently elevated. [ 17 ] Therefore, it is necessary to clarify the impact of HIF‐1α on AD development.…”

Section: Introductionmentioning

confidence: 99%

HIF‐1α Contributes to Hypoxia‐induced VSMC Proliferation and Migration by Regulating Autophagy in Type A Aortic Dissection

Huang,

Chen,

Chen

et al. 2023

Advanced Biology

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Type A aortic dissection (AD) is a catastrophic cardiovascular disease. Hypoxia‐inducible factor‐1α (HIF‐1α) and autophagy are reported to be upregulated in the AD specimens. However, the interaction between HIF‐1α and autophagy in the pathogenesis of AD remains to be explored. HIF‐1α and LC3 levels are evaluated in 10 AD and 10 normal aortic specimens. MDC staining, autophagic vacuoles, and autophagic flux are detected in human aortic smooth muscle cells (HASMCs) under hypoxia treatment. CCK‐8, transwell, and wound healing assay are used to identify proliferation and migration under hypoxia treatment. Furthermore, 3‐MA is used to inhibit autophagy in hypoxia‐treated HASMCs. This study reveals that AD tissues highly express HIF‐1α and the LC3. Autophagy is induced under hypoxia in a time‐dependent manner, and autophagy is positively related to HIF‐1α in HASMCs. Moreover, the proliferation and migration of HASMCs are enhanced by hypoxia, whereas the knockdown of HIF‐1α attenuates this effect. Additionally, inhibiting autophagy with 3‐MA ameliorates hypoxia‐induced proliferation and migration of HASMCs. In summary, the above results indicate that HIF‐1α facilitates HASMC proliferation and migration by upregulating autophagy in a hypoxic microenvironment. Thus, inhibition of autophagy may be a novel therapeutic target for the prevention and treatment of AD.

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Section: Introductionmentioning

confidence: 99%

HIF‐1α Contributes to Hypoxia‐induced VSMC Proliferation and Migration by Regulating Autophagy in Type A Aortic Dissection

Huang,

Chen,

Chen

et al. 2023

Advanced Biology

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“…In addition, some researchers have pointed out that JAK/STAT3-regulated fatty acid β-oxidation is also crucial for BCSC self-renewal and chemotherapy resistance ( 57 ). A study on the mechanism of ASIV have shown that ASIV may relieve myocardial cell damage after hypoxia by activating JAK2/STAT3-mediated HIF-1α signaling ( 58 ). In addition, ASIV can inhibit the Notch signaling pathway and PI3K/Akt/mTOR signaling pathway ( 59 , 60 ).…”

Section: Discussionmentioning

confidence: 99%

Astragaloside IV enhances the sensitivity of breast cancer stem cells to paclitaxel by inhibiting stemness

Huang,

Li,

Ren

et al. 2023

Transl Cancer Res

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Background Chemotherapy is one of the common treatments for breast cancer. The induction of cancer stem cells (CSCs) is an important reason for chemotherapy failure and breast cancer recurrence. Astragaloside IV (ASIV) is one of the effective components of the traditional Chinese medicine (TCM) Astragalus membranaceus , which can improve the sensitivity of various tumors to chemotherapy drugs. Here, we explored the sensitization effect of ASIV to chemotherapy drug paclitaxel (PTX) in breast cancer from the perspective of CSCs. Methods The study included both in vitro and in vivo experiments. CSCs from the breast cancer cell line MCF7 with stem cell characteristics were successfully induced in vitro . Cell viability and proliferation were detected using the Cell Counting Kit-8 (CCK-8) and colony formation assays, and flow cytometry and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) methods were performed to detect cell apoptosis. Stemness-related protein expression was determined by western blotting (WB) and immunohistochemistry (IHC). Body weight, histopathology, and visceral organ damage of mice were used to monitor drug toxicity. Results The expression of stemness markers including Sox2, Nanog, and ALDHA1 was stronger in MCF7-CSCs than in MCF7. PTX treatment inhibited the proliferation of tumor cells by promoting cell apoptosis, whereas the stemness of breast cancer stem cells (BCSCs) resisted the effects of PTX. ASIV decreased the stemness of BCSCs, increased the sensitivity of BCSCs to PTX, and synergistically promoted PTX-induced apoptosis of breast cancer cells. Our results showed that the total cell apoptosis rate increased by about 25% after adding ASIV compared with BCSCs treated with PTX alone. The in vivo experiments demonstrated that ASIV enhanced the ability of PTX to inhibit the growth of breast cancer. WB and IHC showed that ASIV reduced the stemness of CSCs. Conclusions In this study, the resistance of breast cancer to PTX was attributed to the existence of CSCs; ASIV weakened the resistance of MCF7-CSCs to PTX by significantly attenuating the hallmarks of breast cancer stemness and improved the efficacy of PTX.

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“…Notably, this signaling pathway may accomplish signal transduction from extracellular factors to the nucleus ( 27 , 28 ). It has been demonstrated that JAK/STAT signaling pathway is involved in many important physiological activities, such as cell proliferation, differentiation, immune regulation, and apoptosis ( 29 – 31 ).…”

Section: Jak/stat Signaling Pathwaymentioning

confidence: 99%

The potential roles of JAK/STAT signaling in the progression of osteoarthritis

et al. 2022

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Osteoarthritis (OA) is an age-related chronic progressive degenerative disease that induces persistent pain and disabilities. The development of OA is a complex process, and the risk factors are various, including aging, genetics, trauma and altered biomechanics. Inflammation and immunity play an important role in the pathogenesis of OA. JAK/STAT pathway is one of the most prominent intracellular signaling pathways, regulating cell proliferation, differentiation, and apoptosis. Inflammatory factors can act as the initiators of JAK/STAT pathway, which is implicated in the pathophysiological activity of chondrocyte. In this article, we provide a review on the importance of JAK/STAT pathway in the pathological development of OA. Potentially, JAK/STAT pathway becomes a therapeutic target for managing OA.

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Astragaloside IV protects cardiomyocytes against hypoxia injury via HIF-1α and the JAK2/STAT3 pathway

Cited by 9 publications

References 59 publications

HIF‐1α Contributes to Hypoxia‐induced VSMC Proliferation and Migration by Regulating Autophagy in Type A Aortic Dissection

HIF‐1α Contributes to Hypoxia‐induced VSMC Proliferation and Migration by Regulating Autophagy in Type A Aortic Dissection

Astragaloside IV enhances the sensitivity of breast cancer stem cells to paclitaxel by inhibiting stemness

The potential roles of JAK/STAT signaling in the progression of osteoarthritis

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