The Abnomal Expression Of Hepatocyte Growth Factor And Matrix Metalloproteinase-9 In Systemic Lupus Erythematosus And Related Study In Vasculitis

Systemic lupus erythematosus (SLE) is a systemic autoimmune disease, which can cause the damages to multiple organs, including skin, article, chorion, heart, kidney, nerve system and blood system. Although its pathogenesis is not clear so far, the recent studies revealed many important aspects during SLE occurrence and development, including many immunological abnormalities such as abnormal activation of T lymphocyte, polyclonal activation of circulating B lymphocyte that produce a large quantity of autoreactive antibodies and immunity complex deposition. In these processes, many pro-inflammatory chemokines and their receptors play an important regulating role~[1] Inflammatory chemokines and their receptors and some important extracellular matrix were focused on. The further investigation of the roles played by those inflammtory mediators could help to better understand their inductivity and availity in the processes of SLE vasculitis.Hepatocyte growth factor (HGF) is an important inflammatory factor in many kinds of diseases, such as proliferative diabetic retinopathy[2] rheumatoid arthritis and osteoarthritis~[3] HGF can stimulate endothelial mitogenesis, motogenesis and capillary forming~[4] It can activate MAPK (mitogen-actived protein kinase) and PI3K (phosphatidyl inositol-3 kinase) to induce vasculogenesis~[5]. Nakamura and his colleagues ~[6] found that HGF could promote endothelial DNA synthesization and endothelial proliferation in man and rat coronary artery. In order to investigate whether HGF gene can promote blood vessel reconstruction in infarct cardiac muscle, Aoki and his colleagues~[7] embedded HGF gene in infarct cardiac muscle and found obvious endothelial proliferation. But in infarct cardiac muscle with no HGF gene embedded, the concentration of HGF decreased obviously. So it is obvious that HGF gene embedded can increase HGF concentration and promote endothelial proliferation. HGF can also inhibit endothelial apoptosis ~[8] MMP (matrix metalloproteinase) is a modulator for cell growth, migration and extracellular matrix reconstruction~[9] MMP can degrade matrix and provide room for endothelial migration and release growth factors that are isolated by extracellular matrix, such as basic fibroblast growth factor, endothelial growth factor, and insulin-like growth factor~[10] MMP-9, namely gelatinase B~[11], is an important member and its molecular structure is most complicated in MMPs. It can degrade collagens, gelatines and flexibility protein. Because MMP-9 has high affinity with IV collagen and IV collagen is characteristic of endothelial basement membrane, MMP-9 has important role to endothelial structure and function. It has been known that the most important pathologic presentation of SLE isvasculitis. HGF and MMP are thought to be involved in the pathogenesis of SLE vasculitis. Therefore, serum levels of HGF and MMP-9 in SLE and correlationship with the disease activity, renal damages, arthritis, and before and after prednisone therapy were to be investigated in order to study their roles in vasculitis processes and their clinical significance. ECV304 cells (human umbilical vein endothelial cells) were cultivated in vitro to observe the expression of MMP-9 in ECV304 cell when acceding to culture medium with rhHGF (recombinant human hepatocyte growth factor) and the modulating effect of FK506 and minocycline on the expression of MMP-9 in ECV304 cells to provide scientific basis for novel therapy and clinical monitoring in SLE vasculitis. Part I. The detection of serum levels of HGF and MMP-9Serum levels of HGF and MMP-9 were measured by ELISA in 36 patients with SLE. The correlationship between the above-mentioned serum levels and the disease activity, renal damages, and arthritis in those SLE patients were investigated. The data before and after prednisone therapy were also analyzed in order to evaluate clinical significance of the serum levels of HGF and MMP-9 in patients with SLE. Part II. The effect of rhHGF on ECV304 in the expression of MMP-9Because the main pathologic presentation of...