Transforming growth factor-beta in disease: the dark side of tissue repair.

Border, Wayne A.; Ruoslahti, Erkki

doi:10.1172/jci115821

Cited by 1,058 publications

(632 citation statements)

References 78 publications

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“…The mechanisms through which TGF-β1 performs are complex, and involve both the inhibition of epithelial cell proliferation and the development of tissue fibrosis in response to irradiation [3,15,[29][30][31]. The role of TGF-β1 in the progression of human disease and in tissue response to therapy has already been described in great detail [3,7,[12][13][14][15][16][17][18]20,22,[32][33][34].…”

Section: Discussionmentioning

confidence: 99%

Does transforming growth factor-β1 predict for radiation-induced pneumonitis in patients treated for lung cancer?

et al. 2006

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The purpose of the study was to reassess the utility of transforming growth factor-beta-1 (TGF-β1) together with dosimetric and tumor parameters as a predictor for radiation pneumonitis (RP). Of the 121 patients studied, 32 (26.4%) developed grade ≥ 1 RP, and 27 (22.3%) developed grade ≥ 2 RP. For the endpoint of grade ≥ 1 RP, those with V30 > 30% and an end-RT/baseline TGF-β1 ratio ≥ 1 had a significantly higher incidence of RP than did those with V30 > 30% and an end-RT/baseline TGF-β1 ratio < 1. For most other patient groups, there were no clear associations between TGF-β1 values and rates of RP. These findings suggest that TGF-β1 is generally not predictive for RP except for the group of patients with a high V30.

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Section: Discussionmentioning

confidence: 99%

Does transforming growth factor-β1 predict for radiation-induced pneumonitis in patients treated for lung cancer?

et al. 2006

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“…Although rat type I1 (31) and type I11 (30) TGFP receptors have been cloned, no data on the distribution of these molecules in the rat air pouch model are available to date. In addition to interacting with cell surface receptors, TGFP also binds to a number of soluble proteins, such as a,-macroglobulin, soluble decorin and biglycan, thrombospondin, and P-amyloid (30,32). The biologic significance of the binding of TGFP to these molecules is unclear, especially in acute inflammation.…”

Section: Discussionmentioning

confidence: 99%

“…The biologic significance of the binding of TGFP to these molecules is unclear, especially in acute inflammation. However, rats with glomerulonephritis have had improved outcomes after decorin injection (32).…”

Section: Discussionmentioning

confidence: 99%

Inhibition and prevention of monosodium urate monohydrate crystal–induced acute inflammation in vivo by transforming growth factor β1

Lioté

Prudhommeaux

Schiltz

et al. 1996

Arthritis & Rheumatism

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Objective. We investigated the effects of transforming growth factor Pl (TGFP1) on monosodium urate monohydrate (MSU) crystal-induced acute inflammation in vivo.Methods. One hour after MSU crystal-induced acute inflammation was produced in the rat subcutaneous air pouch model, the effects of recombinant human TGFPl (rHuTGFP1; 10-100 pglanimal) and ultrapure TGFPl (UPTGFPI; 100 and 500 pglanimal) were assessed, based on absolute and differential white blood cell counts in the exudate. The effects of 10 pg of rHuTGFP1 preincubated with a specific anti-TGFP antibody, and the effects of coinjection of crystals and rHuTGFP1, were also studied.Results. UPTGFPl and rHuTGFPl markedly reduced MSU crystal-induced inflammation. Recombinant human TGFPl also reduced inflammation when administered concomitantly with MSU crystals. Moreover, rHuTGFPl and UPTGFP1, injected l hour after MSU crystal injection, reduced the inflammatory response in a dose-dependent manner. Injection of rHuTGFPl (100 pglanimal) resulted in a >9w0 reduction in the maximal white blood cell count, achieved 6 hours after Spontaneous resolution is an important clinical feature of gouty attacks that is not yet fully understood (1,2). Lowering of pH and stimulation of phagocyte oxidative metabolism during crystal-induced inflammation may promote monosodium urate monohydrate (MSU) crystal dissolution. However, this cannot entirely explain the self-limited nature of gouty inflammation, since MSU crystals can remain in the synovial fluid after acute inflammation and have been identified in noninflammatory synovial fluids from gout patients (3).In vitro (4) and in vivo ( 5 ) studies have shown that changes in the protein coating of MSU crystals and in other as-yet-unidentified components that are generated locally during subsiding inflammation probably contribute to the self-limited nature of acute gouty arthritis (6). There is strong in vitro evidence that proinflammatory cytokines such as interleukin-lP (ILlP), tumor necrosis factor P (TNFP), IL-6, and IL-8 (7-1 1) are released within hours when monocytes and macrophages are incubated with MSU crystals. Natural cytokine inhibitors such as IL-1 receptor antagonist (IL-1Ra) and/or soluble TNFa receptor, or other regulatory cytokines such as IL-4 and IL-10, may block acute and subsequent chronic inflammation.

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“…It is our hypothesis that inflammatory cell accumulation following tendon-to-bone repair results in this scar interface. Inflammatory cells produce cytokines (such as transforming growth factor+) that are known to stimulate fibroblasts and increase production of extracellular matrix [2]. Identification of strategies to improve tendon-to-bone healing will require definition of the molecular signals (patterns of expression of genes for matrix proteins, transcription factors, cytokines, etc.)…”

Section: Introductionmentioning

confidence: 99%

Macrophages accumulate in the early phase of tendon–bone healing

et al. 2005

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A scar tissue interface forms rather than a normal ligament insertion site following attachment of a tendon graft to bone. The specific cell types that initiate the process of tendon-to-bone healing are unknown. We hypothesized that inflammatory cell accumulation following tendon-to-bone repair results in this scar interface. We used a rodent model to examine the temporal and spatial pattern of accumulation of hematopoietic lineage cells in the early phase of tendon-to-bone healing. Thirty-six Lewis rats underwent anterior cruciate ligament (ACL) reconstruction in the left knee using a flexor digitorum longus tendon graft. Six animals were sacrificed at 4, 7, 11, 14, 21, and 28 days after surgery. Serial sections were analyzed for proliferating cells (PCNA), recruited macrophages (ED1 ), resident macrophages (ED2), neutrophils, T-lymphocytes (CD3), mast cells, immature progenitor cells/pericytes (expressing the NG2 cell-surface chondroitin sulfate proteoglycan), and newly-formed blood vessels (Factor VIII). Neutrbphils, EDlt and ED2+ macrophages accumulated sequentially in the healing tendon graft, with progressive cell ingrowth from the interface towards the inner tendon. Neutrophils and EDl+ cells were seen in the tendon-bone interface at 4 days after surgery, while ED2+ macrophages were not identified until 11 days. These cells progressively repopulated the tendon graft. NG2-positive progenitor cells were found along the edge of the bone tunnel in the interface, but these cells did not invade the tendon. Occasional T-lymphocytes and mast cells were seen in the tendon-bone interface. There was no proliferation of intrinsic tendon cells, indicating that the tendon does not directly contribute to healing. We hypothesize that cytokines produced by infiltrating macrophages are likely to contribute to the formation of a fibrous scar tissue interface rather than a normal insertion site.

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Transforming growth factor-beta in disease: the dark side of tissue repair.

Cited by 1,058 publications

References 78 publications

Does transforming growth factor-β1 predict for radiation-induced pneumonitis in patients treated for lung cancer?

Does transforming growth factor-β1 predict for radiation-induced pneumonitis in patients treated for lung cancer?

Inhibition and prevention of monosodium urate monohydrate crystal–induced acute inflammation in vivo by transforming growth factor β1

Macrophages accumulate in the early phase of tendon–bone healing

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