Impact Of 1,25-?OH?₂D₃ On The Endoplasmic Reticulum Stress And Expression Of ATG12 During The Pathogenesis And Development Of Pulmonary Fibrosis

Objective To investigate the role of endoplasmic reticulum stress and autophagy during the pathogenesis and development of pulmonary fibrosis in rats,and to study the effects of 1,25-(OH)2D3 on the expression of related molecules in endoplasmic reticulum stress and ATG12.Methods 90 male SD rats were randomly divided into control group,model group and treatment group(n =30 each).Bleomycin was injected into the tracheas of rats to establish the model of pulmonary fibrosis in the model group and treatment group.1,25-(OH)2D3 was used to remedy pulmonary fibrosis via intraperitoneal injection.The expression of PERK,ATF4 and ATG12 mRNA were measured by Real-time PCR.The protein expression of PERK and ATF4 were detected by immunohistochemical technology and quantized with image analysis.Results On day 14,the mRNA and protein expression levels of PERK,ATF4 in model group and treatment group were significantly higher than that in control group(P<0.05).Moreover,the expression of mRNA and protein of the two genes increased with the time of modeling,and the difference was statistically significant(P<0.05).on day 14,the mRNA expression level of ATG12 in model group and treatment group were higher than that of control group(P<0.05).However,the mRNA expression level of ATG12 on day 21 and day 28 were reduced obviously compared with control group(P<0.05).The ATG12 mRNA expression on day 28 were slightly decreased compared with that on 21d,but no significant difference was found(P>0.05).In the treatment group,the expression of the three genes were significantly decreased compared with model group at every time point(P<0.05).Conclusion At the early stage of pulmonary fibrosis(14 days),the PERK-eIF2?-ATF4 signaling pathway involved in endoplasmic reticulum stress was activated,accompanying with higher expression of ATG12.With the development of pulmonary fibrosis,the endoplasmic reticulum stress gradually aggravated,while the expression of ATG12 decreased.1,25-(OH)2D3 inhibit the development of pulmonary fibrosis by inhibiting the PERK-eIF2a-ATF4 signaling pathway probably.