title: Mesenchymal stem cells ameliorate inflammatory cytokine-induced impairment of AT-II cells through a keratinocyte growth factor-dependent PI3K/Akt/mTOR signaling pathway.
abstract: Lung epithelium restoration subsequent to injury is of concern in association with the outcomes of diverse inflammatory lung diseases. Previous studies have demonstrated that mesenchymal stem cells (MSCs) may promote epithelial repair subsequent to inflammatory injury, however the mechanism that mediates this effect remains unclear. The current study examined the role of MSCs in alveolar type II epithelial cell (AT‑II cell) restoration subsequent to an inflammatory insult. AT‑II cells were firstly exposed to inflammatory cytokines including tumor necrosis factor‑α, interleukin (IL)‑6 and IL‑1β, then were co‑cultured with MSCs in Transwell for 72 h. Cell proliferation, expression of surfactant protein A (SP‑A) and expression of the α1 subunit were evaluated respectively by the Cell Counting Kit‑8 assay, western blotting and semiquantitative reverse transcription-polymerase chain reaction. Keratinocyte growth factor (KGF) small interfering RNA (siRNA) was applied to knockdown the main cytoprotective factors in the MSCs. Subsequent to an inflammatory insult, AT‑II cells were observed to be impaired, exhibiting the characteristics of injured cell morphology, reduced cell proliferation and reduced expression of SP‑A and the α1 subunit. Co‑culture with MSCs significantly ameliorated these cell impairments, while these benefits were weakened by the application of KGF siRNA. Simultaneously, expression levels of phosphorylated (p‑) protein kinase B (AKT) and p‑mammalian target of rapamycin (mTOR) in AT‑II cells were upregulated by MSCs, suggesting activation of the phosphoinositide 3‑kinase (PI3K) pathway. These data demonstrate that administration of MSCs to the inflammation-insulted AT-II cells may ameliorate the impairments through a KGF-dependent PI3K/AKT/mTOR signaling pathway.
authors.affiliation: Department of Thoracic and Cardiovascular Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China.
authors.forename: Jiwei
authors.initials: J
authors.lastname: Li
authors.affiliation: Key Laboratory of Wound Repair and Regeneration of People's Liberation Army, The First Affiliated Hospital, Trauma Center of Postgraduate Medical College, Beijing 100048, P.R. China.
authors.forename: Sha
authors.initials: S
authors.lastname: Huang
authors.affiliation: Department of Anesthesiology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China.
authors.forename: Junhua
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Thoracic and Cardiovascular Surgery, Peking University People's Hospital, Peking University, Beijing 100044, P.R. China.
authors.forename: Changjiang
authors.initials: C
authors.lastname: Feng
authors.affiliation: Department of Oncology, Dongtai People's Hospital, Dongtai, Jiangsu 224200, P.R. China.
authors.forename: Dongyun
authors.initials: D
authors.lastname: Gao
authors.affiliation: Key Laboratory of Wound Repair and Regeneration of People's Liberation Army, The First Affiliated Hospital, Trauma Center of Postgraduate Medical College, Beijing 100048, P.R. China.
authors.forename: Bin
authors.initials: B
authors.lastname: Yao
authors.affiliation: Department of Thoracic and Cardiovascular Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China.
authors.forename: Xu
authors.initials: X
authors.lastname: Wu
authors.affiliation: Key Laboratory of Wound Repair and Regeneration of People's Liberation Army, The First Affiliated Hospital, Trauma Center of Postgraduate Medical College, Beijing 100048, P.R. China.
authors.forename: Xiaobing
authors.initials: X
authors.lastname: Fu
mesh_terms: D000818:Animals; D004847:Epithelial Cells / Q000378:metabolism* / Q000473:pathology; D051523:Fibroblast Growth Factor 7 / Q000378:metabolism*; D007249:Inflammation / Q000378:metabolism / Q000473:pathology; D008297:Male; D059630:Mesenchymal Stem Cells / Q000378:metabolism* / Q000473:pathology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D011650:Pulmonary Alveoli / Q000378:metabolism* / Q000473:pathology; D037662:Pulmonary Surfactant-Associated Protein A / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*
chemical_list: D051523:Fibroblast Growth Factor 7; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D037662:Pulmonary Surfactant-Associated Protein A; D058570:TOR Serine-Threonine Kinases; C496455:Fgf7 protein, rat; C546845:mTOR protein, rat