| Organic fibrosis are the result of abnormally depositing of extracellular matrix, the mechanism of organic fibrosis is unknown, and the study for quesing the reasonable, operative way to block and even reverse the organic fibrosis is still in difficult groping stage. Since chronic viral hepatitis is common and alcoholic hepatopathy has a rising tendency in our country, the study of the forming mechanism and the methods of diagnosis in early period and effective blocking ways for hepatic fibrosis is still the urgently probles of basic and clinical studies.Our department had devote oneself to study the mechanism of hepatic fibrosis for long-term, our studies together with other researches had proven that the occurrence of organic fibrosis is the result of multiple factor coaction, and the Transforming Growth Factor-p(TGF-p) were the important fibrogenic cytokines.TGF-p is a member of a family of dimeric polypeptide growth factors, and is a multifunctional regulator of cellular activity. There are four isoforms of TGF- : TGF- 1, TGF-P2, TGF-P3, TGF-P1p2 in mammals, each isoform is encoded by a distinct gene and expressed in both tissue-specific and a developmentally regulated fashion. TGF-P 1 is the dominating member in these four isoforms, and has an extensive function, so the study of TGF-P was focusing on TGF-P 1.Transforming Growth Factor-pi (TGF-P 1), a multifunctional regulator of cellular activity, is a 25,000-dalton homodimer molecule that belongs to a family of polypeptides which regulate cell growth, cell differentiation, and cell function. The mature TGF-P 1 homodimer plays a pivotal role in the processes of embryogenesis, adipogenesis, myogenesis, chondrogenesis, osteogenesis, epithelial cell differentiation, and immune cell function.In vitro, TGF-P 1 has an abroad functional activity, which regulate cell function, and plays an important role in the wound healing and tissue repairing. Following wounding andInflammation, Infiltrating cells become the potential sources of TGF-pl. TGF-01 produced and released by these Infiltrating cells regulates the expression of many matrix proteins and inhibit the degradation of these matrix proteins, these actions contribute to tissue repair, which under ideal circumstances leads to the restoration of normal tissue architecture and might involve a component of tissue fibrosis. In many diseases, excessive TGF-pl contribute to a pathologic excess of tissue fibrosis that compromises normal organ function.Since TGF-pl had different actions in different tissue, different organ and different diseases, it had important role to regulate the expression of TGF-pl proteins in different tissues in treatment of diseases.TGF-pl plays a pivotal role in the regulation network of cytokine in vivo, and the biosynthesis and the action of itself is also regulated by many factors, which including cytokines, transcriptional factors, some chemic substance and some medicament. But the molecular mechanism of TGF-pl genie transcription and protein synthesis by these factors had not been clearly defined.The previous studies had indicated that hereditary factors play an impotent role in control of the concentration of TGF-pl in plasma. There were three single nucleotide polymorphisms in the sequence of TGF-pl promoter region, -988OA, -800G>A, -509OT, the two polymorphisms, -800G>A, -509OT, were in linkage disequilibrium, the -509OT polymorphism was significantly associated with the plasma concentration of TGF-pl. The genotypes of different polymorphism in TGF-pl gene sequence were related with the development of several diseases, such as atherosclerosis, cancer and fibrotic diseases. But whether these polymorphisms act through Influencing the activity of TGF-pl promoter is not clearly understood.On the basis of the reasons mentioned above, and to investigate the regulative mechanism of TGF-P1 protein synthesis , the aims of this study were: (1) to construct recombinant plasmids phTGF contain the different length of TGF-P1 promoter region which named phTGF0.585, phTGF1.12, phTGFl.42... |
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