ABSTRACT
BACKGROUND: Organ regeneration in mammals is hypothesized to require a functional pool of stem or progenitor cells, but the role of these cells in lung regeneration is unknown. METHODS: Based on the fact that postnatal regeneration of alveolar tissue has been attributed to alveolar epithelial cells, we established a hemorrhagic shock and Lipopolysaccharide (LPS) lung injury model. Using this model, we analyzed the cellular kinetics of lung alveolar epithelial cells. RESULTS: The results showed that alveolar epithelium type 2 cells (AEC2s) are damage resistant during acute lung injury, they might be the main cells involved in lung injury and repair. Then we observed the relationship between the expression of HGF, c-Met following ALI in rat lung and proliferation of AEC2s. The proliferation of AEC2s was inhibited when isolated primary AEC2s were co-cultured with c-Met inhibitor SU11274. Furthermore, the numbers of AEC2s was significantly decreased when ALI rats were administrated with SU11274 in vivo. It provided further evidence that the HGF/c-Met signaling plays a vital role in ALI-induced AEC2s proliferation. CONCLUSIONS: AEC2s are damage resistant during acute lung injury and the HGF/c-Met signaling pathway is of vital importance in the proliferation of AEC2s after ALI.
Subject(s)
Acute Lung Injury/pathology , Cell Proliferation , Epithelial Cells/pathology , Pulmonary Alveoli/pathology , Regeneration , Acute Lung Injury/chemically induced , Acute Lung Injury/metabolism , Acute Lung Injury/physiopathology , Animals , Cell Proliferation/drug effects , Disease Models, Animal , Epithelial Cells/drug effects , Epithelial Cells/metabolism , Hepatocyte Growth Factor/metabolism , Indoles/pharmacology , Kinetics , Lipopolysaccharides , Male , Piperazines/pharmacology , Protein Kinase Inhibitors/pharmacology , Proto-Oncogene Proteins c-met/antagonists & inhibitors , Proto-Oncogene Proteins c-met/metabolism , Pulmonary Alveoli/drug effects , Pulmonary Alveoli/metabolism , Pulmonary Alveoli/physiopathology , Rats, Sprague-Dawley , Regeneration/drug effects , Signal Transduction , Sulfonamides/pharmacologyABSTRACT
In recent years, more and more research has shown that the lung is an organ of regenerative potential, with several types of stem/progenitor cells undergoing proliferation and differentiation after lung injury and participating the injury repair process. Mouse lung multipotent stem cells (MLSCs) have extensive self-renewal ability in culture and could differentiate into endothelial and lung epithelial (alveolar epithelial type 1, 2, and Clara) cells in vitro. But the research of MLSCs was limited due to its rarity. In this study, we introduced a novel microfluidic magnetic activated cell sorting system in the isolation of MLSCs. The sorted MLSCs had better viability and purity. They were identified by colony formation efficiency and differentiation ability and they have self-renewal and differentiation capacities, highlighting their stem cell properties.
