Transforming Growth Factor Beta-1 in Acute Myocardial Infarction in Rats

Thompson, Nancy L.; Bazoberry, Fernando; Speir, Edith; Casscells, Ward; Ferrans, Víctor J.; Flanders, Kathleen C.; Kondaiah, Patljru; Geiser, Andrew G.; Sporn, Michael B.

doi:10.3109/08977198809000251

Cited by 222 publications

(90 citation statements)

References 15 publications

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“…Furthermore, these synovial tissues expressed increased message levels for TGFX31, implicating an autoinduction of this peptide that may further promote mononuclear cell recruitment and activation . Of interest is the identification of the recently described 1.9-kb species of the TGF01 mRNA, the function of which is unknown, but which has been linked to conditions of tissue injury and inflammation (20,38).…”

Section: Resultsmentioning

confidence: 99%

Rapid onset synovial inflammation and hyperplasia induced by transforming growth factor beta.

Allen

Manthey

Hand

et al. 1990

The Journal of Experimental Medicine

242

131

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Transforming growth factor /3 (TGF (3),t originally isolated from platelets as a 25-kD peptide (1, 2), has been shown to be a product of other inflammatory cells, including lymphocytes (3, 4) and macrophages (5, 6), and to have potent immunomodulatory effects (7). Although five different forms of TGFJ3 have now been characterized (1), only TGF01 and its homologue, TGF02 (8, 9), have thus far been identified in hemopoietic cells (6). Each ofthese peptides has been cloned, demonstrating that TGF01 is encoded as a 390 amino acid precursor (10), TGFs2 as a 412 amino acid precursor (11,12), and that both have a signal peptide of 20-23 amino acids at the NH2 terminus . The processed 112 amino acid chains of the two peptides share 72% sequence homology and appear to bind equally well to TGFS class III receptors (13), although TGFS1 binds with greater affinity than TGF02 to class I and II receptors (14, 15). Interestingly, lymphoid cells appear to possess only class I and II TGF,6 receptors (16), although in vitro, lymphocyte and monocyte responses to TGF01 and 02 appear comparable (6,17,18). The secretion of TGFa peptides by lymphocytes and monocytes only after activation (3-6) implicates these polypeptides in the evolution of immunologic processes, and in recent studies TGFR has been identified in chronic inflammatory tissues (19)(20)(21)(22), including the synovium of rheumatoid arthritis patients (7,22) and in experimentally induced arthritis in rodents (22). To define the role of TGFS in such lesions, we injected natural or recombinant TGF0 directly into the joint cavity of Lewis rats and monitored its effect on cellular recruitment and activation, and on its potential modulation of pathogenic effects. TGF01 and TGF02 were both found to induce synovial erythema, swelling, and leukocyte infiltration . The infiltrating mononuclear cells, activated to express growth factors, likely regulated the pronounced synovial hyperplasia that was apparent within 2-3 d. Based on these observations, it appears that TGF0, released by platelets and inflammatory cells in the arthritic synovium, may directly contribute to the events associated with inflammatory arthropathies.

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Section: Resultsmentioning

confidence: 99%

Rapid onset synovial inflammation and hyperplasia induced by transforming growth factor beta.

Allen

Manthey

Hand

et al. 1990

The Journal of Experimental Medicine

242

131

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“…TGF-β is markedly upregulated in experimental models of myocardial infarction [304]. TGF-β isoforms demonstrate distinct patterns of expression in the infarct: TGF-β1 and -β2 are induced early, whereas TGF-β3 shows delayed and prolonged upregulation [305], [11].…”

Section: Tgf-β Induction and Activation In Cardiac Injurymentioning

confidence: 99%

The immune system and cardiac repair

Frangogiannis

2008

Pharmacological Research

572

499

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Myocardial infarction is the most common cause of cardiac injury and results in acute loss of a large number of myocardial cells. Because the heart has negligible regenerative capacity, cardiomyocyte death triggers a reparative response that ultimately results in formation of a scar and is associated with dilative remodeling of the ventricle. Cardiac injury activates innate immune mechanisms initiating an inflammatory reaction. Toll Like Receptor-mediated pathways, the complement cascade and reactive oxygen generation induce Nuclear Factor (NF)-κB activation and upregulate chemokine and cytokine synthesis in the infarcted heart. Chemokines stimulate the chemotactic recruitment of inflammatory leukocytes into the infarct, while cytokines promote adhesive interactions between leukocytes and endothelial cells, resulting in transmigration of inflammatory cells into the site of injury. Monocyte subsets play distinct roles in phagocytosis of dead cardiomyocytes and in granulation tissue formation through the release of growth factors. Clearance of dead cells and matrix debris may be essential for resolution of inflammation and transition into the reparative phase. Transforming Growth Factor (TGF)-β plays a crucial role in cardiac repair by suppressing inflammation while promoting myofibroblast phenotypic modulation and extracellular matrix deposition. Myofibroblast proliferation and angiogenesis result in formation of highly vascularized granulation tissue. As the healing infarct matures, fibroblasts become apoptotic and a collagen-based matrix is formed, while many infarct neovessels acquire a muscular coat and uncoated vessels regress. Timely resolution of the inflammatory infiltrate and spatial containment of the inflammatory and reparative response into the infarcted area are essential for optimal infarct healing. Targeting inflammatory pathways following infarction may reduce cardiomyocyte injury and attenuate adverse remodeling. In addition, understanding the role of the immune system in cardiac repair is necessary in order to design optimal strategies for cardiac regeneration.

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“…This cytokine not only stimulates the synthesis of individual matrix components, including fibronectin (Ignotz and Massagu, 1986), collagens (Roberts et al, 1986), and proteoglycans (Bassols and Massagu, 1988;Border et al, 1990a), but it also blocks matrix degradation by decreasing the synthesis of proteases and by increasing the levels of protease inhibitors (Edwards et al, 1987;Laiho et al, 1987). Thus, the expression of TGF-␤ may promote the deposition of extracellular matrix (Roberts et al, 1986) and the development of fibrosis (Border and Noble, 1994) in certain types of glomerulonephritis (Okuda et al, 1990), in lung fibrosis (Broekelmann et al, 1991), in liver cirrhosis (Czaja et al, 1989), in cardiac fibrosis after infarction (Thompson et al, 1988), and in scarring disorders of the eye (Connor et al, 1989) and skin (Shah et al, 1992). Elevated renal expression of TGF-␤ has been demonstrated in experimental glomerulonephritis (Coimbra et al, 1991;Okuda et al, 1990) and in several types of human kidney disease (Yamamoto et al, 1993;Yoshioka et al, 1993).…”

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confidence: 99%

Expression of Transforming Growth Factor-β and Tumor Necrosis Factor-α in the Plasma and Tissues of Mice with Lupus Nephritis

Yamamoto

Loskutoff

2000

Laboratory Investigation

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SUMMARY:Although elevated levels of transforming growth factor-␤ (TGF-␤) and tumor necrosis factor-␣ (TNF-␣) have been implicated in renal disease, the tissue distribution and cellular localization of the induced cytokines is not well established. In this study, we investigated the expression of these cytokines during the progression of lupus nephritis in MRL lpr/lpr mice. The concentration of both cytokines increased in the plasma of these animals in an age-dependent manner, and there was an age-dependent induction of TGF-␤ and TNF-␣ mRNAs in their kidneys. Although the increase in TGF-␤ mRNA was specific for the kidney, the increase in TNF-␣ mRNA was widespread and also could be demonstrated in the liver, lung, and heart. In situ hybridization analysis of renal tissues from the lupus-prone mice localized TGF-␤ mRNA to the glomerulus, and more specifically, to resident glomerular cells and inflammatory cells infiltrating periglomerular spaces in the nephritic lesions. The signals for TNF-␣ mRNA were detected only in inflammatory cells and were distributed throughout the nephritic kidney. Plasminogen activator inhibitor-1 (PAI-1) is known to be elevated in the glomeruli of MRL lpr/lpr mice, and intraperitoneal administration of either TGF-␤ or TNF-␣ into normal mice markedly induced the expression of this potent inhibitor of fibrinolysis in renal glomerular or tubular cells in vivo. These results suggest that the increased renal expression of both cytokines may contribute to the development of lupus nephritis in this model and raise the possibility that PAI-1 may be involved. The fact that TGF-␤ is specifically induced in the kidney whereas TNF-␣ increases in a variety of tissues, supports the hypothesis that the renal specificity of this disorder reflects the abnormal expression of TGF-␤. (Lab Invest 2000, 80:1561-1570.L upus nephritis which often accompanies the autoimmune disorder, systemic lupus erythematosus, is characterized by extracellular matrix accumulation and the formation of glomerular, tubular, vascular, and interstitial lesions (Hayslett and Kashgarian, 1993). Inflammatory and immunological processes have been implicated in the development of this nephropathy, including the elaboration of transforming growth factor-␤ (TGF-␤) and tumor necrosis factor-␣ (TNF-␣) (Border and Ruoslahti, 1992;Boswell et al, 1988;Brennan et al, 1989;Moll et al, 1995).TGF-␤ is a multifunctional cytokine that can either inhibit or stimulate cellular proliferation and, as such, seems to play a critical role in tissue repair and regeneration after injury (Border and Ruoslahti, 1992). This cytokine not only stimulates the synthesis of individual matrix components, including fibronectin (Ignotz and Massagu, 1986), collagens (Roberts et al, 1986), and proteoglycans (Bassols and Massagu, 1988;Border et al, 1990a), but it also blocks matrix degradation by decreasing the synthesis of proteases and by increasing the levels of protease inhibitors (Edwards et al, 1987;Laiho et al, 1987). Thus, the expression of TGF-␤ may promote the...

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Transforming Growth Factor Beta-1 in Acute Myocardial Infarction in Rats

Cited by 222 publications

References 15 publications

Rapid onset synovial inflammation and hyperplasia induced by transforming growth factor beta.

Rapid onset synovial inflammation and hyperplasia induced by transforming growth factor beta.

The immune system and cardiac repair

Expression of Transforming Growth Factor-β and Tumor Necrosis Factor-α in the Plasma and Tissues of Mice with Lupus Nephritis

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