Xiuli Tian1, Zhijun Liu2, Ting Yu3, Haitao Yang1, Linlin Feng1. 1. Department of Respiration, Liaocheng People's Hospital, Liaocheng 252000, China. 2. Department of Respiration, Liaocheng People's Hospital, Liaocheng 252000, China. Electronic address: dr_liuzj@sina.com. 3. Department of Ultrasound, Liaocheng People's Hospital, Liaocheng 252000, China.
Abstract
AIMS: Acute lung injury (ALI) is associated with excessive mortality and lacks appropriate therapy. Ghrelin is a novel peptide that protects the lung against ALI. This study aimed to investigate whether endoplasmic reticulum stress (ERS) mediates the protective effect of ghrelin on ALI. MAIN METHODS: We used a rat oleic acid (OA)-induced ALI model. Pulmonary impairment was detected by hematoxylin and eosin (HE) staining, lung mechanics, wet/dry weight ratio, and arterial blood gas analysis. Plasma and lung content of ghrelin was examined by ELISA, and mRNA expression was measured by quantitative real-time PCR. Protein levels were detected by western blot. KEY FINDINGS: Rats with OA treatment showed significant pulmonary injury, edema, inflammatory cellular infiltration, cytokine release, hypoxia and CO2 retention as compared with controls. Plasma and pulmonary content of ghrelin was reduced in rats with ALI, and mRNA expression was downregulated. Ghrelin (10nmol/kg) treatment ameliorated the above symptoms, but treatment with the ghrelin antagonists D-Lys3 GHRP-6 (1μmol/kg) and JMV 2959 (6mg/kg) exacerbated the symptoms. ERS induced by OA was prevented by ghrelin and augmented by ghrelin antagonist treatment. The ERS inducer, tunicamycin (Tm) prevented the ameliorative effect of ghrelin on ALI. The decreased ratio of p-Akt and Akt induced by OA was improved by ghrelin treatment, and was further exacerbated by ghrelin antagonists. SIGNIFICANCE: Ghrelin protects against ALI by inhibiting ERS. These results provide a new target for prevention and therapy of ALI.
AIMS: Acute lung injury (ALI) is associated with excessive mortality and lacks appropriate therapy. Ghrelin is a novel peptide that protects the lung against ALI. This study aimed to investigate whether endoplasmic reticulum stress (ERS) mediates the protective effect of ghrelin on ALI. MAIN METHODS: We used a ratoleic acid (OA)-induced ALI model. Pulmonary impairment was detected by hematoxylin and eosin (HE) staining, lung mechanics, wet/dry weight ratio, and arterial blood gas analysis. Plasma and lung content of ghrelin was examined by ELISA, and mRNA expression was measured by quantitative real-time PCR. Protein levels were detected by western blot. KEY FINDINGS:Rats with OA treatment showed significant pulmonary injury, edema, inflammatory cellular infiltration, cytokine release, hypoxia and CO2 retention as compared with controls. Plasma and pulmonary content of ghrelin was reduced in rats with ALI, and mRNA expression was downregulated. Ghrelin (10nmol/kg) treatment ameliorated the above symptoms, but treatment with the ghrelin antagonists D-Lys3 GHRP-6 (1μmol/kg) and JMV 2959 (6mg/kg) exacerbated the symptoms. ERS induced by OA was prevented by ghrelin and augmented by ghrelin antagonist treatment. The ERS inducer, tunicamycin (Tm) prevented the ameliorative effect of ghrelin on ALI. The decreased ratio of p-Akt and Akt induced by OA was improved by ghrelin treatment, and was further exacerbated by ghrelin antagonists. SIGNIFICANCE: Ghrelin protects against ALI by inhibiting ERS. These results provide a new target for prevention and therapy of ALI.
Authors: Jens Kamuf; Andreas Garcia-Bardon; Alexander Ziebart; Rainer Thomas; Robert Rümmler; Christian Möllmann; Erik K Hartmann Journal: J Vis Exp Date: 2018-10-26 Impact factor: 1.355
Authors: S Ezquerro; S Becerril; C Tuero; L Méndez-Giménez; F Mocha; R Moncada; V Valentí; J A Cienfuegos; V Catalán; J Gómez-Ambrosi; K Piper Hanley; G Frühbeck; A Rodríguez Journal: Int J Obes (Lond) Date: 2019-07-19 Impact factor: 5.095