| [Background] Interstitial lung disease(ILD) is a type of fibrosing lungdisease of known deleterious causes in environment or other unknown etiologywhich is related to immunological dysfunction. One of the most common and byfar the most aggressive ILD is idiopathic pulmonary fibrosis (IPF), whichrepresents a chronic, progressive and usually lethal lung disorder. Microphagesof alveolus, together with T cells and epithelial cells which build a complicatedextracellular crossing talking by expressing a variety of cytokines and growthfactors involved in fibroblast migration, proliferation, and in extracellular matrixremodeling. This pathological process together with the disruption of theepithelial basement membrane enhances the migration of fibroblasts into thealveolar spaces and the subsequent accumulation of intra-alveolar extracellularmatrix. Studies of bleomycin induced pulmonary fibrosis in rats havedemonstrated that in IPF lungs, matrix metalloproteinases and most cytokines,such as platelet-derived growth factor, transforming growth factor beta ,tumornecrosis factor alpha, connective tissue growth factor, and endothelin-1,may induce epithelial cell apoptosis, basement membrane disruption andaberrant extracellular matrix remodeling.Matrix metalloproteinases (MMPs), also known as matrixins, are membersof a family of Zn-dependent endopeptidases which derived from normal cells,inflammatory cells and tumorous cells that are responsible for degradation ofvarious protein components of the intercellular matrix and basal membranes atneutral PH values. The subfamily of gelatinases includes gelatinase A (MMP-2,72KD) and gelatinase B (MMP-9, 92KD). Gelatinases cleave type â…£ andelastin inside basal membranes and de-natured collagen(gelatin). Due to thelatter property, gelatinases comple-ment collagenases during the degradation offibrillar collagens. So far, 25 different human MMPs have been characterizedincluding data on their primary structure. Physiological processes involvingremodeling of the extracellular matrix, such as wound healing, embryogenesis,angiogenesis, and the female reproductive cycle, require the activity of matrixmetalloproteinases (MMPs). This group of proteases degrades basal membranesand connective tissues and plays an essential role in the homeostasis of theextracellular matrix.An imbalance in the expression or activity of MMPs can have importantconsequences in diseases such as interstitial lung diseases (ILD), arthritis,multiple sclerosis, Alzhermer's disease, or the development of cancers. Becauseof the pathophysiological importance of MMPs, their activity is highlycontrolled in order to confine them to specific areas. An activation cascade,initiated by the proteolysis of plasmmogen, cleaves proMMPs, and every step iscontrolled by specific activators or inhibitors. MMPs destabilize the organi-zation of the extracellular matrix and influence the development of cancer bycontributing to cell migration, tumor cell proliferation, and angiogenesis.Accordingly, these proteases possess an important role in cell-matrix inter-actions by affecting fundamen-tal processes such as cell differentiation andproliferation. Therefore, the characterization of MMPs involved in specific typeswill significantly improve the diagnosis and treatment of clinical diseases inhumans.Moreover, recent studies focus on the effect of adrenal cortical hormone ortissue inhibitors of metalloproteinases (TIMPs) on pulmonary interstitial fibrosis.Recent evidence strongly suggests that Adrenal cortical hormone can suppresspulmonary fibrosis and inflammation . At present, the natural choice fortreatment has been the use of corticosteroids and other immunosuppressivedrugs. And that is also a effective drug therapy for acute interstitial pneumonia.However, there is little studies on mechanism of using corticosteroids in humanIPF. Accordingly, it is very important to research on interaction of matrixmetalloproteinases, especially on the interaction of gelatinase A, gelatinase Band most cytokines. Therapies designed to inhibit fibroblast proliferation andECM accumulation are now being evaluated. Larger confirmatory trials are nowrunning and in the near future we will know how good these drugs are for IPFpatients.[Objectives] To investigate the change of expression of ProMMP-9,MMP-9, ProMMP-2 and MMP-2 in serum of patients with idiopathic pulmonaryfibrosis in early disease who were before using glucocorticoid, also 3 months and6 months after that, and to evaluate the function of MMPs in idiopathicpulmonary fibrosis and Its Clinical Significance.[Methods] The expression of ProMMP-9, MMP-9, ProMMP-2 and MMP-2were examined by SDS-PAGE zymograph in 37 IPF patients who werebefore using glucocorticoid, also 3 months and 6 months after that, comparingwith the expression of normal persons.[Results] Compared with the normal persons, the expression of ProMMP-9,MMP-9, ProMMP-2 and MMP-2 were much higher in IPF1 patients who were inearly disease before using glucocorticoid(P<0.05), the expression of ProMMP-9,MMP-9, ProMMP-2 and MMP-2 were reduced in IPF2 and IPF3 patients who hadused hormone for 3 or 6 months (P>0.05).[Conclusions] The expression of MMPs in serum of IPF patientssuggested that MMPs might play an important role in the immunochemicalprocess of lung damnification and restore. It provides a new method for diagnosis,treatment and judging prognosis in molecular side. Then the great bulk of studieson MMPs are designed to find new inhibitors in the future. |
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