ArticleEBioMedicine2018
PI3Kγ promotes vascular smooth muscle cell phenotypic modulation and transplant arteriosclerosis via a SOX9-dependent mechanism.
Article in EBioMedicine, 2018. 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, 26 citations in OpenAlex.
- Effects and mechanisms of trifolin on attenuating hypertension-induced vascular smooth muscle cell proliferation and collagen deposition in vivo and in vitro.Scientific reports · 2025Article
- The perspective of modern transplant science - transplant arteriosclerosis: inspiration derived from mitochondria associated endoplasmic reticulum membrane dysfunction in arterial diseases.International journal of surgery (London, England) · 2025Review
- Molecular mechanisms and therapeutic progress in atherosclerosis: bridging immune inflammation and precision medicine.Frontiers in immunology · 2025Review
- SOX9 mediates the phenotypic transformation of vascular smooth muscle cells in restenosis after carotid artery injury.Frontiers in cell and developmental biology · 2025Article
- Prevention of neointimal hyperplasia after coronary artery bypass graft via local delivery of sirolimus and rosuvastatin: network pharmacology and in vivo validation.Journal of translational medicine · 2024Article
- Sox9 Accelerates Vascular Aging by Regulating Extracellular Matrix Composition and Stiffness.Circulation research · 2024Article
- KIF11 promotes vascular smooth muscle cell proliferation by regulating cell cycle progression and accelerates neointimal formation after arterial injury in mice.Frontiers in pharmacology · 2024Article
- Sox9 mediates autophagy-dependent vascular smooth muscle cell phenotypic modulation and transplant arteriosclerosis.iScience · 2022Article
- The Effects of CD73 on Gastrointestinal Cancer Progression and Treatment.Journal of oncology · 2022Review
- CCAAT/Enhancer-Binding Protein Alpha Is a Novel Regulator of Vascular Smooth Muscle Cell Osteochondrogenic Transition and Vascular Calcification.Frontiers in physiology · 2022Article
- TNFα and Reactive Oxygen Signaling in Vascular Smooth Muscle Cells in Hypertension and Atherosclerosis.American journal of hypertension · 2020Review
- CD73 sustained cancer-stem-cell traits by promoting SOX9 expression and stability in hepatocellular carcinoma.Journal of hematology & oncology · 2020Article
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Authors and funding
15 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundTransplant arteriosclerosis (TA) remains the major cause of chronic graft failure in solid organ transplantation. The phenotypic modulation of vascular smooth muscle cells (VSMCs) is a key event for the initiation and progression of neointimal formation and TA. This study aims to explore the role and underlying mechanism of phosphoinositide 3-kinases γ (PI3Kγ) in VSMC phenotypic modulation and TA.
methodsThe rat model of aortic transplantation was established to detect PI3Kγ expression and its role in neointimal formation and vascular remodeling in vivo. PI3Kγ shRNA transfection was employed to knockdown PI3Kγ gene. Aortic VSMCs was cultured and treated with TNF-α to explore the role and molecular mechanism of PI3Kγ in VSMC phenotypic modulation.
findingsActivated PI3Kγ/p-Akt signaling was observed in aortic allografts and in TNF-α-treated VSMCs. Lentivirus-mediated shRNA transfection effectively inhibited PI3Kγ expression in medial VSMCs while restoring the expression of VSMC contractile genes, associated with impaired neointimal formation in aortic allografts. In cultured VSMCs, PI3Kγ blockade with pharmacological inhibitor or genetic knockdown markedly abrogated TNF-α-induced downregulation of VSMC contractile genes and increase in cellular proliferation and migration. Moreover, SOX9 located in nucleus competitively inhibited the interaction of Myocardin and SRF, while PI3Kγ inhibition robustly reduced SOX9 expression and its nuclear translocation and repaired the Myocardin/SRF association.
interpretationThese results suggest that PI3Kγ plays a critical role in VSMC phenotypic modulation via a SOX9-dependent mechanism. Therefore, PI3Kγ in VSMCs may represent a promising therapeutic target for the treatment of TA. FUND: National Natural Science Foundation of China.
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