RETRACTED ARTICLE: Effect of hCMSCs and liraglutide combination in ALI through cAMP/PKAc/β-catenin signaling pathway

Yun Feng,Linlin Wang,Xiaoying Ma,Xiaotong Yang,Ocholi Don,Xiaoyan Chen,Jieming Qu,Yuanlin Song

doi:10.1186/s13287-019-1492-6

Abstract

BackgroundALI/ARDS is the major cause of acute respiratory failure in critically ill patients. As human chorionic villi-derived MSCs (hCMSCs) could attenuate ALI in the airway injury model, and liraglutide, glucagon-like peptide 1 (GLP-1) agonist, possesses anti-inflammatory and proliferation promotion functions, we proposed to probe the potential combinatory effect of hCMSCs and liraglutide on ALI.MethodsWe examined the time- and dose-dependent manner of GLP-1R, SPC, Ang-1, and FGF-10 with LPS via western blot and qRT-PCR. Western blot and chromatin immunoprecipitation assay detected the effects of liraglutide on GLP-1R, SPC, Ang-1, and FGF-10 through PKAc/β-catenin pathway and cAMP pathway. In the ALI animal model, we detected the effects of MSC and liraglutide combination on ALI symptoms by H&E staining, western blot, ELISA assays, calculating wet-to-dry ratio of the lung tissue, and counting neutrophils, leukocytes, and macrophages in mouse bronchoalveolar lavage fluid (BALF).ResultsThe data demonstrated that LPS reduced hCMSC proliferation and GLP-1R, SPC, Ang-1, and FGF-10 levels in a dose- and time-dependent manner. Liraglutide significantly dampened the reduction of GLP-1R, SPC, Ang-1, and FGF-10 and reversed the effect of LPS on hCMSCs, which could be regulated by GLP-1R and its downstream cAMP/PKAc/β-catenin-TCF4 signaling. Combination of hCMSCs with liraglutide showed more therapeutic efficacy than liraglutide alone in reducing LPS-induced ALI in the animal model.ConclusionsThese results reveal that the combination of hCMSCs and liraglutide might be an effective strategy for ALI treatment.

Highlights

Acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) is the major cause of acute respiratory failure in critically ill patients
LPS induces GLP-1 receptor (GLP-1R) expression in a dose- and timedependent manner The expression of GLP-1R was evaluated by the qRTPCR, which was corrected with GAPDH as an internal control
The expression of surfactant protein C (SPC), Ang-1, and FGF-10 were reduced during LPS stimulation We investigated whether LPS stimulation could affect SPC, Ang-1, and FGF-10 expression

Summary

Introduction

ALI/ARDS is the major cause of acute respiratory failure in critically ill patients. Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) would result in acute respiratory failure and high mortality in critically ill patients [1, 2]. The features of ALI/ARDS are the alveolar-capillary membrane barrier injury, leukocyte accumulation, lung edema, inflammation, and alveolar hemorrhage [1, 3]. A growing number of studies have found that transplantation of MSC was an attractive cell therapy candidate for ALI [5], intracerebral hemorrhage [6], osteogenic differentiation capacity [7], and Alzheimer’s disease [8]. Mounting evidence showed that MSC could reduce inflammation and fibrosis and attenuate lung repair in ALI models [9, 10]. Many studies have been performed to investigate strategies of increasing efficacy and differentiation of MSC [14,15,16,17]

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