Transition of autophagy and apoptosis in fibroblasts depends on dominant expression of HIF-1α or p53

Li, Min; Su, Yidan; Gao, Xiaoyuan; Yu, Jiarong; Wang, Zhiyong; Wang, Xiqiao

doi:10.1631/jzus.b2100187

Cited by 9 publications

(11 citation statements)

References 36 publications

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“…Moreover, it was shown that HIF‐1α‐induced autophagy contributed to DDP resistance in ovarian cancer cell line OVCAR‐3 28 . Nevertheless, HIF‐1α downregulation inhibited autophagy and induced apoptosis in human dermal fibroblasts 29 . Overexpression of HIF‐1α substantially improved the resistance of ovarian cancer cells to DDP, whereas Baohuoside I decreased the expression of HIF‐1α in a dose‐dependent manner.…”

Section: Discussionmentioning

confidence: 97%

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Baohuoside I inhibits resistance to cisplatin in ovarian cancer cells by suppressing autophagy via downregulating HIF‐1α/ATG5 axis

Zhou

Liu

et al. 2023

Molecular Carcinogenesis

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Since chemotherapy's therapeutic impact is diminished by drug resistance, treating ovarian cancer is notably challenging. Thereafter, it is critical to develop cutting‐edge approaches to treating ovarian cancer. Baohuoside I (derived from Herba Epimedii) is reported to have antitumor properties in various malignancies. It is unknown, however, what role Baohuoside I plays in cisplatin (DDP)‐resistant ovarian cancer cells. 3‐(4,5)‐dimethylthiahiazo (‐z‐y1)‐3,5‐di‐phenytetrazoliumromide (MTT), colony formation, and flow cytometry assay were used to investigate the impact of Baohuoside I on ovarian cancer A2780 cells and DDP‐resistant A2780 (A2780/DDP) cells. The level of microtubule associated protein 1 light chain 3 (LC3) was determined using immunofluorescence staining. Utilizing the mRFP‐GFP‐LC3B tandem fluorescent probe allowed us to analyse the autophagy flux. Analysis of mRNA and protein level was performed using RT‐qPCR and Western blot analysis, respectively. The interaction between hypoxia inducible factor 1 subunit alpha (HIF‐1α) and autophagy related 5 (ATG5) promoter was investigated by dual luciferase and ChIP assay. Additionally, evaluation of Baohuoside I's role in ovarian cancer was performed using a nude mouse xenograft model. Baohuoside I decreased the viability and proliferation and triggered the apoptosis of both A2780 and A2780/DDP cells in a concentration‐dependent manner. Baohuoside I also increased the sensitivity of A2780/DDP cells to DDP. Concurrently, HIF‐1α could promote A2780/DDP cells resistance to DDP. In addition, HIF‐1α could induce the autophagy of A2780/DDP cells through transcriptionally activating ATG5, and Baohuoside I imporved the chemosensitivity of A2780/DDP cells to DDP by downregulating HIF‐1α. Moreover, Baohuoside I could inhibit the chemoresistance to DDP in ovarian cancer in vivo. Baohuoside I sensitizes ovarian cancer cells to DDP by suppressing autophagy via downregulating the HIF‐1α/ATG5 axis. Consequently, Baohuoside I might be evaluated as a new agent for enhancing the chemotherapeutic efficacy of drug treatment for ovarian cancer.

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Section: Discussionmentioning

confidence: 97%

“…28 Nevertheless, HIF-1α downregulation inhibited autophagy and induced apoptosis in human dermal fibroblasts. 29 Autophagy activation induced drug resistance in malignant tumors, according to prior research. [30][31][32] The upregulation of ATG5 can promote the formation of autophagosomes, making it a crucial regulator of autophagy.…”

Section: Discussionmentioning

confidence: 99%

Baohuoside I inhibits resistance to cisplatin in ovarian cancer cells by suppressing autophagy via downregulating HIF‐1α/ATG5 axis

Zhou

Liu

et al. 2023

Molecular Carcinogenesis

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“…Li et al found that p53 was downregulated under hypoxia. It made p53 difficult to combine with p300, promoting HIF‐1α more easily to combine with p300 and exert its transcriptional effect 105 . Overall, the pathophysiological mechanisms of HIF‐1α in hypertrophic scars are not completely known.…”

Section: Biological Effects Of Hif‐1α In Different Cells: Promoting K...mentioning

confidence: 99%

Role of HIF‐1α in pathogenic mechanisms of keloids

Qiu

Zhang

et al. 2023

J of Cosmetic Dermatology

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Backgrouds and Objective Keloids are defined as overrepairing products that develop after skin lesions. Keloids are characterized by the proliferation of fibroblasts and the overaccumulation of extracellular matrix components (mainly collagen), leading to a locally hypoxic microenvironment. Hence, this article was aimed to review hypoxia in pathogenesis of keloids. Methods We reviewed and summarized the relevant published studies. Results Hypoxia results in the accumulation of hypoxia‐inducible factor 1α (HIF‐1α) in keloids, contributing to overactivation of the fibrotic signaling pathway, epithelial–mesenchymal transition, and changes in metabolism, eventually leading to aggravated fibrosis, infiltrative growth, and radiotherapy resistance. Conclusion It is, therefore, essential to understand the role of HIF‐1α in the pathogenic mechanisms of keloids in order to develop new therapeutic approaches.

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“…; https://doi.org/10.1101/2023.02. 23.529661 doi: bioRxiv preprint Several studies have revealed the role of miR-195-3p in cardiovascular diseases, but its role in hypoxia-induced ECs remains unidentified.…”

Section: Micrornas (Mirnas) Are Endogenous Non-coding Rnas Approximat...mentioning

confidence: 99%

“…The "Anaerobic tank method" was used to establish the hypoxia model. The expression of HIF-1a in HUVECs (22,23) was analyzed to confirm the successful establishment of an in vitro hypoxia model. The experimental results confirmed that hypoxia injury weakened the proliferation, migration, and autophagy of HUVECs and promoted the apoptosis of HUVECs.…”

Section: Mir-195-3p Inhibitor Rescued the Apoptosis Of Hypoxia Injure...mentioning

confidence: 99%

MicroRNA-195-3p as a potential regulator of hypoxic injury in HUVECs

Zhang

Liu

Wang

et al. 2023

Preprint

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Coronary heart disease is the most common heart disease and is the leading cause of cardiovascular death worldwide. Revascularization methods are considered effective against coronary heart disease However, the mechanism of molecular revascularization remains largely unknown. Endothelial cells are the primary cells that initiate angiogenesis and arteriogenesis and require a hypoxic environment for induction. In this study, we aimed to determine the expression and role of microRNA-195-3p in hypoxia-treated HUVEs (human umbilical vein endothelial cells). Herein, we induced hypoxia in human umbilical vein endothelial cells using the "Anaerobic tank method." Hypoxia injured human umbilical vein endothelial cells showed upregulation of microRNA-195-3p; decreased cell proliferation, migration, and autophagy; and increased apoptosis. Furthermore, the microRNA-195-3p inhibitor partially reversed the effects of hypoxia-induced injury of human umbilical vein endothelial cells. Therapeutic intervention using microRNA-195-3p inhibitor could maintain endothelial cell function under hypoxic conditions, improve cell activity, and be considered a new treatment strategy for coronary heart diseases.

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Transition of autophagy and apoptosis in fibroblasts depends on dominant expression of HIF-1α or p53

Cited by 9 publications

References 36 publications

Baohuoside I inhibits resistance to cisplatin in ovarian cancer cells by suppressing autophagy via downregulating HIF‐1α/ATG5 axis

Baohuoside I inhibits resistance to cisplatin in ovarian cancer cells by suppressing autophagy via downregulating HIF‐1α/ATG5 axis

Role of HIF‐1α in pathogenic mechanisms of keloids

MicroRNA-195-3p as a potential regulator of hypoxic injury in HUVECs

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