ArticleCell proliferation2021
ERK/Drp1-dependent mitochondrial fission contributes to HMGB1-induced autophagy in pulmonary arterial hypertension.
Article in Cell proliferation, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 76 papers.
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Who cites it
76 citing papers in PubMed, 131 citations in OpenAlex.
- Nr4a3 deficiency disrupts MEK1-ERK1/2-Drp1 signaling, driving adiposity and glucose intolerance in male mice.American journal of physiology. Endocrinology and metabolism · 2026Article
- Autophagy-Targeted Vascular Remodeling in Pulmonary Arterial Hypertension: Molecular Mechanisms and Therapeutic Perspectives.Journal of cardiovascular development and disease · 2026Review
- HMGB1 impairs nasal epithelial barrier via regulating autophagy in the pathogenesis of allergic rhinitis.The World Allergy Organization journal · 2026Article
- Post-translational modifications of mitochondrion-related proteins: integrative orchestrators of cell fate networks in cardiovascular disease.Cell communication and signaling : CCS · 2026Review
- HMGB1 drives pulmonary arterial smooth muscle cell proliferation and migration via the MAP2K3/p38 pathway in pulmonary vascular remodeling.Scientific reports · 2026Article
- The Role of Stress Granules in Cardiovascular Diseases.Reviews in cardiovascular medicine · 2026Review
- HMGB1 blockade attenuates cardiac injury induced by radiotherapy combined with PD-1 inhibitor while maintaining the anti-tumor efficacy.Apoptosis : an international journal on programmed cell death · 2026Article
- PAK5 drives vascular remodeling in hypoxic pulmonary hypertension via Drp1-dependent mitochondrial midzone division.Scientific reports · 2026Article
- Mitochondrial acid-sensing ion channel 1a deficiency induces mitochondrial dysfunction in pulmonary arterial smooth muscle cells.American journal of physiology. Lung cellular and molecular physiology · 2026Article
- Interleukin-6 Signaling Mediates Mitochondrial Fragmentation and Mitophagy Impairment to Induce Macrophages Ferroptosis in Atherosclerosis.Inflammation · 2026Article
- Paradigm shift: from pulmonary vasodilation to cardiopulmonary dual-track therapy-a comprehensive review of pathophysiology and advances in pulmonary hypertension-associated right heart failure.Respiratory research · 2026Review
- Exercise-mediated regulation of mitochondrial dynamics in aging muscle: implications for mitochondrial diseases.Molecular and cellular biochemistry · 2026Review
- Article
- Super enhancer-driven LINC01013 mediates hypoxia-induced mitochondrial dysfunction by HSPA9 to determine pulmonary arterial smooth muscle cell fate.Cellular and molecular life sciences : CMLS · 2026Article
- Role of Perturbations of Epigenetic Processes in Cardiac Hypertrophy and Fibrotic Scarring.Current cardiology reviews · 2026Review
- Beta-Alanine Supplementation Ameliorates Right Ventricular Remodeling Caused by Monocrotaline-Induced Pulmonary Hypertension.Pulmonary circulation · 2026Article
- Inhibitor of DNA binding 1 in lung cancer and the tumor microenvironment: a testable hypothesis for malignant pleural effusion formation.Frontiers in immunology · 2026Review
- HMGB1: a multifaceted mediator of cell death pathways in cardiovascular diseases.Apoptosis : an international journal on programmed cell death · 2025Review
- HMGB1 and mitochondrial dysfunction: a double-edged sword in ageing.Open biology · 2025Review
- Nobiletin alleviates hypoxia-induced pulmonary hypertension by inhibiting calcium-sensing receptor.Journal of natural medicines · 2025Article
16 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
13 authors at 1 institution in 1 country.
Funding
Abstract
objectivesHigh-mobility group box-1 (HMGB1) and aberrant mitochondrial fission mediated by excessive activation of GTPase dynamin-related protein 1 (Drp1) have been found to be elevated in patients with pulmonary arterial hypertension (PAH) and critically implicated in PAH pathogenesis. However, it remains unknown whether Drp1-mediated mitochondrial fission and which downstream targets of mitochondrial fission mediate HMGB1-induced pulmonary arterial smooth muscle cells (PASMCs) proliferation and migration leading to vascular remodelling in PAH. This study aims to address these issues.
methodsPrimary cultured PASMCs were obtained from male Sprague-Dawley (SD) rats. We detected RNA levels by qRT-PCR, protein levels by Western blotting, cell proliferation by Cell Counting Kit-8 (CCK-8) and EdU incorporation assays, migration by wound healing and transwell assays. SD rats were injected with monocrotaline (MCT) to establish PAH. Hemodynamic parameters were measured by closed-chest right heart catheterization.
resultsHMGB1 increased Drp1 phosphorylation and Drp1-dependent mitochondrial fragmentation through extracellular signal-regulated kinases 1/2 (ERK1/2) signalling activation, and subsequently triggered autophagy activation, which further led to bone morphogenetic protein receptor 2 (BMPR2) lysosomal degradation and inhibitor of DNA binding 1 (Id1) downregulation, and eventually promoted PASMCs proliferation/migration. Inhibition of ERK1/2 cascade, knockdown of Drp1 or suppression of autophagy restored HMGB1-induced reductions of BMPR2 and Id1, and diminished HMGB1-induced PASMCs proliferation/migration. In addition, pharmacological inhibition of HMGB1 by glycyrrhizin, suppression of mitochondrial fission by Mdivi-1 or blockage of autophagy by chloroquine prevented PAH development in MCT-induced rats PAH model.
conclusionsHMGB1 promotes PASMCs proliferation/migration and pulmonary vascular remodelling by activating ERK1/2/Drp1/Autophagy/BMPR2/Id1 axis, suggesting that this cascade might be a potential novel target for management of PAH.
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