Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0034069 (pulmonary fibrosis)
 7,050 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Fibroblast migration, proliferation, extracellular matrix protein synthesis and degradation are the key events in various biological and pathological processes in pulmonary fibrosis. In addition, biopsy specimens from the lungs of patients with pulmonary fibrosis show increased numbers of mast cells which have metachromatic granules containing heparin, histamine and proteases. Little is known about how these products influence pulmonary fibrosis. In the present study, we investigated the effect of heparin and related glycosaminoglycans on PDGF-induced lung fibroblast proliferation and chemotactic response in vitro. In addition, we examined the effect of heparin on both the induction of matrix metalloproteinases (MMPs) and MMPs activity in lung fibroblasts in vitro. Heparin, de-N-sulphated heparin but not heparan sulphate inhibited PDGF-induced lung fibroblast proliferation. In contrast, only heparin inhibited PDGF-stimulated human lung fibroblast chemotaxis. Negatively charged poly-L-glutamic acid had no effect on either fibroblast proliferation or chemotaxis. Thus the negative charge alone cannot account for the ant-proliferative and anti-chemotactic effects of heparin. Furthermore, heparin and heparan sulphate also had no inhibitory effect on induction of MMPS, including MMP-1 (interstitial collagenase), MMP-2 (gelatinase A) and MMP-9 (gelatinase B). Only heparin inhibited both MMP-1 and MMP-2/MMP-9 activity. Additionally, tissue inhibitor of metalloproteinase type 1 (TIMP-1) and type 2 (TIMP-2) inhibited PDGF-stimulated human lung fibroblast chemotaxis. The ability of heparin to inhibit fibroblast chemotaxis may account for the inhibitory effect of heparin on MMP activity. The above results suggested that heparin and related glycosaminoglycans differentially regulate PDGF-induced lung fibroblast proliferation, chemotaxis and MMPs activity and further that these effects may have a key role in extracellular matrix remodeling in inflammatory lung disease.
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PMID:Effect of heparin and related glycosaminoglycan on PDGF-induced lung fibroblast proliferation, chemotactic response and matrix metalloproteinases activity. 1095 81

The mast cell has been a fundamental focus for nearly half a century in the effort to understand the biology of the cysteinyl leukotrienes (cysLTs). My initial interest in the cysLTs, once termed the slow reacting substance of anaphylaxis (SRS-A), was based on the findings of others that this activity was elaborated by lung tissue and constricted bronchial smooth muscle in the presence of an antihistamine. We now know that leukotriene C4 (LTC4) is formed when arachidonic acid is cleaved from membrane phospholipids, and metabolized to an epoxide intermediate, LTA4 that in turn is conjugated to reduced glutathione by an integral membrane protein, LTC4 synthase. The LTC4 is exported in an energy-dependent step and subjected to extracellular cleavage of the glutamic acid and then the glycine to provide LTD4 and LTE4, respectively. Mice with targeted disruption of the LTC4S gene are partially protected against plasma leakage elicited in the ear by adaptive immune mast cell activation or in the peritoneal cavity by microbial carbohydrate stimulation of the macrophages. Such mice are also partially protected against pulmonary fibrosis after intratracheal administration of bleomycin. A strain with targeted disruption of the CysLT1 receptor gene is protected against the pathobiological insults that augment microvascular permeability, whereas a strain with targeted disruption of the CysLT2 receptor gene is protected against pulmonary fibrosis. Thus, the expression of these receptors on endothelium, smooth muscle and cells of the haematopoietic lineage such as mast cells, macrophages, and granulocytes extends the possible role of this lipid mediator pathway to both acute and chronic inflammation.
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PMID:The mast cell and the cysteinyl leukotrienes. 1660 34