Medical Application And Molecular Mechanism Of Human Hair Keratin

The expression of TGFp 1, 2, 3 mRNA and distribution of ubiquitin, laminin and VEGF different weeks after implantation of man-made tendon HHK were studied in the first part of this thesis. It was found that TGF0K 2 may play critical roles in tendon healing, TGFP3 cooperates with them. Degeneration of HHK keratin may mainly be intermediated by ubiqutin. Lysosome plays role in clearance of abnormal protein in newly generated tissue near HHK, ubuquitin also takes part in this process. In newly generated tendon tissue, there were large amount of fibroblasts , VEGF and LN were highly expressed. The number of fibroblasts, and the amounts of VEGF, LN decreased in nearly mature and mature tendon tissues. LN was mainly secreted by fibroblasts, inflammatory cells and macrophages could also produce LN, 6 weeks after HHK implantation. LN is propitious to formation of intercellular tight junction, bundle the collagen fibrils to come into being tendon.The sencond part is about the research on the repair of injured tibial nerve by conduits made of human hair keratin (HHK) and its mechanism involved. Tibial nerves of rabbits received operation were transected to create 10 mm gap, linked by suture, without conduit (group II), or the both nerve stumps were inserted into the conduit's lumen, the epineurium of the nerve stumps were sutured with conduits, with 9-0 nylon (group III). Electrophysiological, anatomic and histological examinations were done in different days after surgery. Conduit made of human hair keratin can guide tibial nerve elongation across a 1 Omm gap. HHK is a kind of perfect material for nerve conduit. HHK and its degenerated product can induce the formation of NGF and P75, create a suitable micro-environment for nerve regeneration. Suture has not such function. More NGF and P75 were produced in newly generated nerve tissue than that in mature nerve tissue. Transection of nerve can elevate the amount of LN. LN is mainly produced by Shwann cells in peripheral nerve tissue, as an important ingredient of excellular matrix, it could provide appropriate adherence for elongation of nerve fibres. VEGF may mainly secreted by epineurial fibroblasts and Shwaan cells, it has not only the function ofvasculogenesis, but also neurogenesis. Degeneration of HHK and abnormal proteins in denatured tissue between sutures may mainly be intermediated by ubiquitin. There are more ubiqitin which take part in clearance of abnormal proteins in newly generated nerve tissue, less in nearly mature nerve tissue.Expression difference of genes between human bone marrow mesenchymal stem cells and tendon cells was studied in the third part by hybridization of cDNA probes reverse-transcripted from total RNA and cDNA Array produced by CLONTECH. Expression level of fifteen genes(AIMl, HNGS1 , DYRK3, KIAA015K BCAT, uroporphyringen III synthase, GAS, GDFKK ZYX, JAK2, CHRM4, STATK LIGK MLF2, VIL2) were up-regulated, these genes are associated with cell proliferation and signal transduction; one gene(LERK2) which takes part in cell to cell adhesion were down-regulated in tendon cells, among the 1176 genes detected.