The Expression Of TGF-βⅠR Subtypes In Lung Fibrosis

Background:Interstitial lung disease /pulmonary fibrosis is a serious risk to human health, the incidence rate is in a gradually ascending trend. The pathological process includes inflammation cells invading, collagen depositing, amounts of excellular matrix assembling in the mesenchyma, resulting in reformation of the lung structure. At present, there is no effective treatment in term of the unknown etiology and unclear pathogenesis. Although it is difficult to eliminate formation of pulmonary fibrosis, pulmonary fibrosis is a chronic, progressive pathological process. The strategies by exploring the molecular mechanism of the pathogenesis and new intervention target in delaying or blocking the progression of pulmonary fibrosis still have important practical significance and have been always a focus for the pneumo-science circle .TGF-βis a key cytokine in fibrosis. The definite mechanism is that activated TGF-βbinding to the typeⅡreceptor (RⅡ) leads to recruitment of the typeⅠreceptor (RⅠ) and formation of the receptor heterocomplex. In the complex, the constitutively active typeⅡreceptor phosphorylates the typeⅠreceptor at GS domain and actives it. The activated typeⅠreceptor is then able to bind and phosphorylate Smads protein. But the effect and mechanism of TGF-βⅠtype receptor and subtypes has not been understood. So the purpose of the study is to sieve the specific subtypes in the lung fibrosis. In this study, we explore the specific subtypes that exist in normal lung and pulmonary fibrosis by analyzing the distribution and changes of the subsets of TGF-βⅠR,to delay or block pulmonary fibrosis .Objective:To identify the distribution and expressive changes of the subsets of TGF-βⅠR in normal lung and pulmonary fibrosis. To explore the specific subtypes in pulmonary fibrosis, analysis the distribution and changes of the subsets of TGF-βⅠR in normal lung and pulmonary fibrosis synthetically and provide the new evidence for curing the lung fibrosis.Method:We established fibrosis models, identified the distribution and expressive changes of the subsets of TGF-βⅠR in normal lung and pulmonary fibrosis through Real Time-PCR, and selected the specific subtypes in the lung fibrosis combining with pathology.Result:1. Pathologic change by HE staining:HE staining showed that various kinds of inflammatory cells infiltrated in alveolus and pulmonary mesenchyme, the most obvious in the 7th group. Lung fibroblast began to increase in the 14th group. The fibrosis was clearer in the 28th group, the clearest in the 35th group, with alveolus atrophy and destruction.2. Real Time-PCR:Compared with normal group, the mRNA levels of ALK-4,ALK-5 and ALK-7 were significantly increased in the rat model of fibrosis established, but the ones of ALK-1 and ALK-2 were not marked.The mRNA levels of ALK-3 and ALK-6 were increased in the early stage and then inclined in the process of lung fibrosis.Using repeated measurements analysis of variance, comparing the expressive changes between groups at different time point, we concluded that the results were P<0.05 significantly.Conclusion:1. ALK1-7 participated in the process of lung fibrosis.2. The expression of ALK-4,ALK-5 and ALK-7 was more obvious than other subtypes in the process of lung fibrosis.Their relative concentrations were raised up to more than five times.