ArticleJournal of orthopaedic surgery and research2021
The role of activating transcription factor 6 in hydroxycamptothecin-induced fibroblast autophagy and apoptosis.
Article in Journal of orthopaedic surgery and research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 87 citations in OpenAlex.
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- Cemented total knee arthroplasty provides greater knee range of motion at 2 years than cementless technique.European journal of orthopaedic surgery & traumatology : orthopedie traumatologie · 2023Review
- Disparities in the Epidemiology and Management of Fragility Hip Fractures.Current osteoporosis reports · 2023Review
- Patella non-resurfacing in primary total knee arthroplasty provides good functional results-a retrospective review of nine thousand three hundred forty six knees.International orthopaedics · 2023Article
- Spinal cord compression in thoracolumbar burst fractures: application of high-definition three-dimensional exoscope in minimally invasive lateral surgery.European journal of orthopaedic surgery & traumatology : orthopedie traumatologie · 2023Review
- Dual role of endoplasmic reticulum stress-ATF-6 activation in autophagy and apoptosis induced by cyclic stretch in myoblast.Apoptosis : an international journal on programmed cell death · 2023Article
- Regulation of cardiac fibroblast cell death by unfolded protein response signaling.Frontiers in physiology · 2023Review
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundThe over-proliferation of fibroblasts is considered to be the main cause of scar adhesion after joint surgery. Hydroxycamptothecin (HCPT), though as a potent antineoplastic drug, shows preventive effects on scar adhesion. This study aimed to investigate the role of activating transcription factor 6 (ATF-6) in the HCPT-induced inhibition of fibroblast viability.
methodsThe cell counting kit-8 (CCK-8) assay, western blot analysis, lentivirus-mediated gene silencing, transmission electron microscopy (TEM) analysis, immunofluorescent staining for autophagy-related protein light chain 3 (LC3) were used to explore the effect of HCPT on triggering fibroblast apoptosis and inhibiting fibroblast proliferation, and the involvement of possible signaling pathways.
resultsIt was found that HCPT exacerbated fibroblast apoptosis and repressed its proliferation. Subsequently, endoplasmic reticulum stress (ERS)-related proteins were determined by western blot prior to ATF6 p50 was screened out and reexamined after it was silenced. As a result, ATF6-mediated ERS played a role in HCPT-induced fibroblast apoptosis. Autophagy-related proteins and autophagosomes were detected after the HCPT administration using western blot and TEM analyses, respectively. Autophagy was activated after the HCPT treatment. With the co-treatment of autophagy inhibitor 3-methyladenine (3-MA), both the western blot analysis and the CCK-8 assay showed inhibited autophagy, which indicated that the effect of HCPT on fibroblast proliferation was partially reversed. Besides, the LC3 immunofluorescence staining revealed suppressed autophagy after silencing ATF6 p50.
conclusionOur results demonstrate that HCPT acts as a facilitator of fibroblast apoptosis and inhibitor of fibroblast proliferation for curbing the postoperative scar adhesion, in which the ATF6-mediated ERS pathway and autophagy are involved.
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