دورية أكاديمية
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mTORC2 Activation Mediated by Mesenchymal Stem Cell-Secreted Hepatocyte Growth Factors for the Recovery of Lipopolysaccharide-Induced Vascular Endothelial Barrier

التفاصيل البيبلوغرافية
العنوان: mTORC2 Activation Mediated by Mesenchymal Stem Cell-Secreted Hepatocyte Growth Factors for the Recovery of Lipopolysaccharide-Induced Vascular Endothelial Barrier
المؤلفون: Shan-Shan Meng, Feng-Mei Guo, Li-Li Huang, Ying-Zi Huang, Jian-Feng Xie, Cong-Shan Yang, Hai-Bo Qiu, Yi Yang
المصدر: Stem Cells International, Vol 2021 (2021)
بيانات النشر: Wiley, 2021.
سنة النشر: 2021
المجموعة: LCC:Internal medicine
مصطلحات موضوعية: Internal medicine, RC31-1245
الوصف: Acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) is characterized by pulmonary microvascular endothelial barrier dysfunction. Mesenchymal stem cell-secreted hepatocyte growth factor (HGF) has positive effects of lipopolysaccharide- (LPS-) induced pulmonary endothelial barrier. Studies have exhibited the mammalian TORC1 (mTORC1) signaling is of potent angiogenesis effects. The mTOR protein kinase has two distinct multiprotein complexes mTORC1 and mTORC2 that regulate different branches of the mTOR network. However, detailed mTORC2 mechanisms of HGF protective effects remain poorly defined. Therefore, the aim of this study was to determine whether mTORC2 mediated protective effects of MSC-secreted HGF against LPS-induced pulmonary microvascular endothelial barrier dysfunction activated like mTORC1 activation. We introduced MSC-PMVEC coculture transwell system and recombinant murine HGF on LPS-induced endothelial cell barrier dysfunction in vitro and then explored potential mechanisms by lentivirus vector-mediated HGF, mTORC1 (raptor), and mTORC2 (rictor) gene knockdown modification. Endothelial paracellular and transcellular permeability, adherent junction protein (VE-Cadherin), cell proliferation, apoptosis, and mTOR-associated proteins were tested. These revealed that HGF could promote quick reestablishment of adherent junction VE-cadherin and decrease endothelial paracellular and transcellular permeability during LSP-induced endothelial dysfunction with the involvement of mTORC2 (rictor) and mTORC1 (raptor) pathways. Raptor and rictor knockdown in LPS-induced PMEVECs with stimulation of HGF increased apoptosis ratio, activated Cleaved-Caspase-3 expression, and downregulated cell proliferation. Moreover, mTORC2/Akt but not mTORC2/PKC had significance on HGF endothelial protective effects. Taken together, these highlight activation mTORC2 pathway could also contribute to vascular endothelial barrier recovery by MSC-secreted HGF in LPS stimulation.
نوع الوثيقة: article
وصف الملف: electronic resource
اللغة: English
تدمد: 1687-966X
1687-9678
Relation: https://doaj.org/toc/1687-966X; https://doaj.org/toc/1687-9678
DOI: 10.1155/2021/9981589
URL الوصول: https://doaj.org/article/133676956f5741cfbeefd9c95490e5aa
رقم الأكسشن: edsdoj.133676956f5741cfbeefd9c95490e5aa
قاعدة البيانات: Directory of Open Access Journals
الوصف
تدمد:1687966X
16879678
DOI:10.1155/2021/9981589