Tranforming Growth Factor-βs And Receptor Expression In Lesional Skin And Peripheral Blood Of Psoriasis With Their Significance

Psoriasis is a multifactorial inheritance disease with immunity abnormality, involve in infection, trauma, mind stress and so on. Psoriasis is characterized by three main pathogenic features: keratinocyte hyperproliferation, abnormal differentiaton, and inflammation in dermal. In several years, The study which are about promote epidermal hyperproliferation is very much , such as epidermal growth factor(EGF) , keratinocyte growth factor(KGF) and transforming growth factor- a (TGF- a )and so on . But as these for therapy target, ideal results are not acquired. More and more facts prove psoriasis may be the result about abnormal network of cytokines. That psoriasis whether exist in down regulation of transforming growth factor-3 (TGF-J3) for suppressing keratinocyte growth? Transforming growth factor-13 of cytokines is the name given to a family of multifunctional polypeptides. It has many biological effects including regulation of cellular proliferation, differentiation, migration, extracellular matrix (ECM) formation, and modulation of the immune response. Some studys reveal TGF-~3 is down regulation of keratinocyte growth .In mammalian, three are known isoforms respectively TGF-j3 1, TGF-j32, and TGF-p3. TGF-s exert their biological effects via binding specific receptors. The receptors include three types , respectively type I receptor(TGF-pR I ) , type II receptor(TGF-~R II) ,and type III receptor(TGF-~3RJII) . TGF-f3R I and TGF-f3R II are serine/threonine kinases .Their structure is same, but numbers of amino acid are not same. TGF-113R I and TGF-13R II ,both of which are required for TGF-~3 signalling through the receptor complex. Initially ,autophosphorylation of TGF-f3R II binds to TGF-13, the type I receptor recognize ligand-bound type II receptor,forming an oligomeric complex ,and then transfer signal . The type III receptor is aslo called betaglycan , it has not kinase activity ,and not take part in signaling transduction . Its function increases the TGF-p binding to the receptor type H ,but not TGF-~3 binding to TGF-pR I ,its function as a regulator of TGF-f3 access to the signaling heteromeric kinase receptor complex formed by TGF-j3 receptor components I and II .Endoglin(CD1O5)is a major binding protein ?- 第二军医大学博士学位论文 高春芳 for transforming growth factor－p．It Is a homodlmerlc membrane glycoproteln composed ofdisulfide－linked subunits of95阴a．Endoglln shares regions ofsequence ldentltywlth betaglycan(TGFNlll)．Itbinds TGF－gi and TGF－63 with hbo affinity but fat！s to bind TGF－pZ．It prevents TGF－p to binding receptors,retain TGF－p In the intracellular matrix, or make Inactlvatlon of TGF－p,and can reduce the bioavailability of TGF－p．In brie不 TGF－ps and their receptors with binding protein exert biological effects by coordination． It Is negative modulation of＊thetion immune response,bm It Is also positive modulation of＊thetion immune response· In abroad,some stUdies h。e shown that transforming growth factor－p receptor binding and function are decreased In psorlatlc dermal mlcrovascular endothelial cells (DMEC),These in vitro inding suggest that reduction of TGF－p receptor expression and function may contribute to Iymphocyte Infiltration Into psorlatlc piNnes In vlvo by allowing dermal mlcrovascular endothellum to escape rom the negative regulation by TGF－9．In our country there are no studies about this．Besides,...