ArticleActa pharmacologica Sinica2019
Crosstalk between the Akt/mTORC1 and NF-κB signaling pathways promotes hypoxia-induced pulmonary hypertension by increasing DPP4 expression in PASMCs.
Article in Acta pharmacologica Sinica, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.
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56 citing papers in PubMed.
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- Viral-host interactions mediated by the mTOR signaling pathway.Cell insight · 2026Review
- Cellular Signalling Networks in High Altitude Pulmonary Hypertension: From Canonical Pathways to Emerging Targets.Cell proliferation · 2026Review
- Review of the Effects of Anesthetic Techniques and Medications on the Immune Response During the Perioperative Period.Medical science monitor : international medical journal of experimental and clinical research · 2026Review
- PPIL1 promotes hepatocellular carcinoma progression and associates with poor prognosis.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Targeting Inflammation-Oxidative Stress Crosstalk: Advances and Challenges in Nanocarrier-Based Interventional Strategies for Pulmonary Arterial Hypertension.International journal of nanomedicine · 2026Review
- NF-κB signaling as a critical inflammatory node in pulmonary arterial hypertension: from vascular remodeling to right heart failure.Frontiers in immunology · 2026Review
- Flavonoids: Potential New Drug Candidates for Attenuating Vascular Remodeling in Pulmonary Hypertension.International journal of molecular sciences · 2025Review
- Exploring the protective role of DDIT4/mTOR in podocyte integrity through macrophage polarization in diabetic kidney disease.Renal failure · 2025Article
- NF-κB and pulmonary hypertension: Advances in mechanistic research and therapeutic applications.American heart journal plus : cardiology research and practice · 2025Review
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- Peroxiredoxin 4 as a switch regulating PTEN/AKT axis in alveolar macrophages activation.Signal transduction and targeted therapy · 2025Article
- Combined Treatment with Evogliptin and Temozolomide Alters miRNA Expression but Shows Limited Additive Effect on Glioma.International journal of molecular sciences · 2025Article
- Albumin Reduces Hepatic Steatosis and Inflammation in High-Fat-Diet-Fed Mice.International journal of molecular sciences · 2025Article
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16 authors.
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Abstract
Abnormal wound healing by pulmonary artery smooth muscle cells (PASMCs) promotes vascular remodeling in hypoxia-induced pulmonary hypertension (HPH). Increasing evidence shows that both the mammalian target of rapamycin complex 1 (mTORC1) and nuclear factor-kappa B (NF-κB) are involved in the development of HPH. In this study, we explored the crosstalk between mTORC1 and NF-κB in PASMCs cultured under hypoxic condition and in a rat model of hypoxia-induced pulmonary hypertension (HPH). We showed that hypoxia promoted wound healing of PASMCs, which was dose-dependently blocked by the mTORC1 inhibitor rapamycin (5-20 nM). In PASMCs, hypoxia activated mTORC1, which in turn promoted the phosphorylation of NF-κB. Molecular docking revealed that mTOR interacted with IκB kinases (IKKs) and that was validated by immunoprecipitation. In vitro kinase assays and mass spectrometry demonstrated that mTOR phosphorylated IKKα and IKKβ separately. Inhibition of mTORC1 decreased the level of phosphorylated IKKα/β, thus reducing the phosphorylation and transcriptional activity of NF-κB. Bioinformatics study revealed that dipeptidyl peptidase-4 (DPP4) was a target gene of NF-κB; DPP4 inhibitor, sitagliptin (10-500 μM) effectively inhibited the abnormal wound healing of PASMCs under hypoxic condition. In the rat model of HPH, we showed that NF-κB activation (at 3 weeks) was preceded by mTOR signaling activation (after 1 or 2 weeks) in lungs, and administration of sitagliptin (1-5 mg/kg every day, ig) produced preventive effects against the development of HPH. In conclusion, hypoxia activates the crosstalk between mTORC1 and NF-κB, and increased DPP4 expression in PASMCs that leads to vascular remodeling. Sitagliptin, a DPP4 inhibitor, exerts preventive effect against HPH.
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