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Myocardial fibrosis is a critical event during septic shock. Upregulation in the fibrosis signaling cascade proteins such as fibroblast growth factor (FGF), urokinase plasminogen activator (uPA), tissue plasminogen activator (tPA) and activation of matrix metalloproteinases (MMPs) are widely associated with the development of myocardial infarction, dilated cardiomyopathy, cardiac fibrosis and heart failure. However, evidences suggest that the common upstream mediators of fibrosis cascade play little role in cardiac fibrosis induced by LPS; further, it is unknown if LPS directly triggers the expressions and/or activity of FGF-2, uPA, tPA, MMP-2 and MMP-9 in cardiac fibroblasts. In the present study, we treated primary cultures of cardiac fibroblasts with LPS to explore whether LPS upregulates FGF-2, uPA, tPA, MMP-2, MMP-9 and enhance cellular migration. Further the precise molecular and cellular mechanisms behind these LPS induced responses were identified. Inhibition assays on MAPKs using U0126 (ERK1/2 inhibitor), SB203580 (p38 MAPK inhibitor), SP600125 (JNK1/2 inhibitor), CsA (calcineurin inhibitor) and QNZ (NFκB inhibitor) show that LPS-induced upregulation of FGF-2, uPA, MMP-2 and MMP-9 in cardiac fibroblasts was mediated through ERK1/2 signaling. Collectively, our results provide a link between LPS-induced cardiac dysfunction and ERK1/2 signaling pathway and thereby implies ERK1/2 as a possible target to regulate LPS induced upregulation of FGF-2, uPA, MMP-2, MMP-9 and cellular migration in cardiac fibroblasts.
This article was published in the following journal.
Name: Chemico-biological interactions
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The main objective of this study is to investigate safety, tolerability, pharmacokinetics and pharmacodynamics of oral BI 1026706, administered for 4 weeks, on lipopolysaccharide-induced i...
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It has been reported that volatile anesthetics preconditioning mediates protection of organ via microRNA. We want to study on the effects of isoflurane preconditioning on expression of mic...
Vitiligo is the most common acquired depigmented disorder of the skin characterized by destruction of melanocytes resulting in well-circumscribed achromic macules. Ultraviolet phototherapy...
Protein factor(s) released by sensitized lymphocytes (and possibly other cells) that inhibit the movement of LEUKOCYTES, especially polymorphonuclear cells, away from their site of release. Assays for these factors are used as tests for cellular immunity. Two of the common assays are the LEUKOCYTE MIGRATION CAPILLARY TUBE TECHNIQUE (LMCT) and the LEUKOCYTE MIGRATION AGAROSE TEST (LMAT).
Glycolipid-anchored membrane glycoproteins expressed on cells of the myelomonocyte lineage including MONOCYTES; MACROPHAGES; and some GRANULOCYTES. They function as receptors for the complex of lipopolysaccharide (LPS) and LPS-binding protein.
Abnormally low BODY TEMPERATURE that is intentionally induced in warm-blooded animals by artificial means. In humans, mild or moderate hypothermia has been used to reduce tissue damages, particularly after cardiac or spinal cord injuries and during subsequent surgeries.
The lipopolysaccharide-protein somatic antigens, usually from gram-negative bacteria, important in the serological classification of enteric bacilli. The O-specific chains determine the specificity of the O antigens of a given serotype. O antigens are the immunodominant part of the lipopolysaccharide molecule in the intact bacterial cell. (From Singleton & Sainsbury, Dictionary of Microbiology and Molecular Biology, 2d ed)
A disorder of cardiac function secondary to hypersensitivity reactions. It is characterized by coexistence of acute coronary syndromes and cardiac MAST CELL and PLATELET ACTIVATION. It may be induced by exposure to drugs (e.g., antibiotics, anesthetics, contrast media), food, and environmental triggers (e.g., insect bites and stings, poison ivy).
Immunoassay - ELISA
Immunoassays are quick and accurate tests to detect specific molecules. Immunoassays rely on an antibody to bind to the specific structure of a molecule. Antibodies are proteins generated by animals in response to the invasion of a foreign molecule (anti...