Mesenchymal stem cells ameliorate LPS-induced acute lung injury through KGF promoting alveolar fluid clearance of alveolar type II cells

摘要

OBJECTIVE: It has been shown that Mesenchymal stem cells (MSCs) could prevent or alleviate acute lung injury (ALI) when transplanted into lung; however, the mechanisms involved remains elusive. The study aimed to investigate the effect of MSCs in repairing alveolar fluid clearance (AFC) of alveolar type-II (AT-II) cells through paracrine factors. MATERIALS AND METHODS: Keratinocyte growth factor (KGF) concentration in the supernatant of MSC culture medium was measured, and MSCs in lung after intravenous administration was traced. Next, MSCs transfected with or without KGF SiRNA were injected intravenously into LPS-induced ALI rats. Histological change and wet/dry ratio were determined. AT-II cells were co-cultured with MSCs under different experimental situations to analyze the variation of α1 and β1 subunits of Na+-K+-ATPase in AT-II cells. RESULTS: LPS-induced ALI was characterized by the typical inflammatory infiltrates, interalveolar septal thickening and increased wet/dry ratio. MSC administration significantly reduced the injury, while MSCs with KGF knockdown did no show the same effect. In vitro study also confirmed that expressions of α1 and β1 subunit were up-regulated as impaired AT-II cells co-cultured with MSCs. Furthermore, expression of α1 subunit was down-regulated, while β1 subunit showed no apparent change as AT-II cells were co-cultured with MSCs that were transfected with KGF siRNA. CONCLUSIONS: AFC was impaired by inflammation insult. MSCs-derived KGF reduced the impaired AFC through up-regulated α1 subunit but not β1 subunit, which might provide a novel therapeutic strategy for ALI.