Altered expression of small proteoglycans, collagen, and transforming growth factor-beta 1 in developing bleomycin-induced pulmonary fibrosis in rats.

Westergren‐Thorsson, Gunilla; Hernnäs, J; Särnstrand, Bengt; Oldberg, Åke; Heinegård, Dick; Malmström, Anders

doi:10.1172/jci116631

Cited by 211 publications

(137 citation statements)

References 35 publications

(30 reference statements)

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“…Furthermore, there is strong evidence for a role for TGF-␤ in diseases characterized by accumulation of excess amounts of extracellular matrix such as mesangial injury in the rat model of glomerulonephritis (22), diabetic nephropathy in humans (43), cirrhosis of the liver both in rats and humans (38), and in muscular fibrosis seen in patients with Duchenne muscular dystrophy (44). Overproduction of TGF-␤ also has been linked to fibrotic pulmonary processes such as bleomycin-induced pulmonary fibrosis in rats (24,45), as well as lung pathology in humans with idiopathic pulmonary fibrosis (46) and sarcoidosis (47).…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

In vitrorestoration of T cell responses in tuberculosis and augmentation of monocyte effector function againstMycobacterium tuberculosisby natural inhibitors of transforming growth factor β

Hirsch

Ellner

Blinkhorn

et al. 1997

Proc. Natl. Acad. Sci. U.S.A.

126

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We examined the capacity of the naturally occurring inhibitors of transforming growth factor ␤ (TGF-␤), decorin and latency associated peptide (LAP), to reverse depressed T cell functions in peripheral blood mononuclear cells (PBMCs) from patients with pulmonary tuberculosis (TB) in vitro and to counteract the suppressive properties of TGF-␤ on mycobacterial replication in blood monocytes (MN) in vitro. T cell blastogenesis in response to purified protein derivative (PPD) in PBMCs of TB patients that were cocultured with decorin or LAP reached levels comparable to those observed in healthy tuberculin-responsive control subjects. Decorin and LAP were as effective as neutralizing antibody to TGF-␤ in correcting depressed T cell proliferation. Coculture of PBMCs from healthy PPD reactive individuals with neutralizing antibody to TGF-␤, decorin, or LAP did not affect T cell blastogenesis. Levels of interferon-␥ in cultures of PPDstimulated PBMCs from patients with TB increased by more than 2-fold in the presence of maximal concentrations of either of the inhibitors of TGF-␤, whereas TGF-␤ immunoreactivity declined to background levels. Coculture with optimal concentrations of decorin or LAP also led to reductions in mycobacterial growth in MN infected with Mycobacterium tuberculosis (MTB) in vitro by 51% and 62%, respectively, when compared with cells left untreated. In parallel, levels of immunoreactive TGF-␤ in MTB-infected MN cultures containing decorin or LAP decreased to background levels. These data indicate that the naturally occurring inhibitors of TGF-␤, decorin and LAP, efficiently abrogate the suppressive effects of TGF-␤ in PBMCs of TB patients and in MN infected with MTB in vitro. Therefore, these agents may be considered as adjuncts to antituberculous chemotherapy, and may be particularly useful in treatment of TB that is unresponsive to conventional chemotherapy.

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Section: Discussionmentioning

confidence: 99%

“…Inactivation of TGF-␤ bioactivity by decorin is thought to involve binding of the decorin core protein to the active TGF-␤ molecule (23). Decorin is expressed along with TGF-␤ in pulmonary tissue of rats with bleomycin-induced pulmonary fibrosis (24) and may play a role in counteracting the profibrotic tendencies of the TGF-␤.…”

mentioning

confidence: 99%

In vitrorestoration of T cell responses in tuberculosis and augmentation of monocyte effector function againstMycobacterium tuberculosisby natural inhibitors of transforming growth factor β

Hirsch

Ellner

Blinkhorn

et al. 1997

Proc. Natl. Acad. Sci. U.S.A.

126

View full text Add to dashboard Cite

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“…In spite of the presence of all TGF-␤ polypeptides and the presence of components of the TGF-␤ signaling pathways, the precise role of TGF-␤ in lung morphogenesis or repair following injury remains unclear. In adult mouse and human, TGF-␤1 mRNA and protein levels increased in macrophages, fibroblasts and alveolar epithelial cells following lung injury (Westergren-Thorsson et al, 1993;Finkelstein et al, 1994;Coker et al, 1997), suggesting that TGF-␤1 may be a mediator of cell proliferation, inflammation and extracellular matrix production associated with tissue repair and remodeling. Injury to the lung of premature infants causes bronchopulmonary dysplasia (BPD), a severe form of lung disease affecting preterm infants.…”

Section: Introductionmentioning

confidence: 99%

TGF‐β1 perturbs vascular development and inhibits epithelial differentiation in fetal lung in vivo

Zeng

Gray

Stahlman

et al. 2001

Developmental Dynamics

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Members of the transforming growth factor ␤ (TGF-␤) family of polypeptides have been implicated in morphogenesis and differentiation in numerous tissues, including the lung. In order to further define effects of TGF-␤ signaling in lung morphogenesis, a constitutively active form of TGF-␤1 was expressed in respiratory epithelial cells of the fetal mouse lung in vivo. Expression of TGF-␤1 arrested lung morphogenesis in the pseudoglandular stage of development, inhibiting synthesis of differentiation-dependent proteins, SP-B, SP-C, and CCSP, and maintaining embryonic patterns of staining for thyroid transcription factor-1 (TTF-1) and hepatocyte nuclear factor-3␤ (HNF-3␤). The pulmonary mesenchyme was thickened and vascular density was increased by TGF-␤1. TGF-␤1 decreased expression of vascular endothelial growth factor-A (VEGF-A) mRNA and protein, and the abundance of Flk-1 mRNA in the lung mesenchyme. Distribution of platelet-endothelial cell adhesion molecule (PECAM)-1, a marker of pulmonary blood vessels, was altered, and ultrastructural studies demonstrated that TGF-␤1 inhibited vascular development in the fetal lung. TGF-␤1 perturbed both epithelial cell differentiation and formation of the pulmonary vasculature, supporting the concept that precise control of signaling via the TGF-␤ receptor pathway is critical for normal lung morphogenesis.

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“…TGF-is considered to be a major fibrogenic cytokine [6,7] and has been implicated in the generation of pulmonary fibrosis in humans [5]. In rats with pulmonary fibrosis induced by the administration of bleomicyn, total TGF-1 content was several times higher than in normal rats, and increased production of TGF-1 preceded the synthesis of ECM components [8].…”

Section: Introductionmentioning

confidence: 99%

Release of transforming growth factor-beta (TGF-β) and fibronectin by alveolar macrophages in airway diseases

Vignola¹,

Chanez

Chiappara³

et al. 1996

Clinical and Experimental Immunology

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SUMMARYAsthma and chronic bronchitis are associated with airway remodelling, and airway macrophages are present in bronchial inflammation. TGF-¯and fibronectin released by alveolar macrophages possess a fibrogenic potency. The potential role of alveolar macrophages in airway remodelling was studied in asthma and chronic bronchitis by the release of TGF-¯and fibronectin. Alveolar macrophages were isolated by bronchoalveolar lavage in 14 control subjects, 14 asthmatics and 14 chronic bronchitics. The spontaneous and lipopolysaccharide (LPS)-or concanavalin A (Con A)-induced release of TGF-¯and fibronectin was measured by ELISA. Alveolar macrophages from chronic bronchitics spontaneously release greater amounts of TGF-¯and fibronectin than those from asthmatic and control subjects. Alveolar macrophages from asthmatics release greater amounts of TGF-¯and fibronectin than those from control subjects. The spontaneous release of TGF-¯is significantly correlated with that of fibronectin. Fibronectin release was significantly reduced after LPS stimulation, and TGF-¯release was significantly increased after LPS stimulation, except in chronic bronchitis patients. Con A increased the release of TGF-¯in cells from normal subjects. This study suggests that activated macrophages play a role in airway remodelling in chronic bronchitis and to a lesser extent in asthma.

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Altered expression of small proteoglycans, collagen, and transforming growth factor-beta 1 in developing bleomycin-induced pulmonary fibrosis in rats.

Cited by 211 publications

References 35 publications

In vitrorestoration of T cell responses in tuberculosis and augmentation of monocyte effector function againstMycobacterium tuberculosisby natural inhibitors of transforming growth factor β

In vitrorestoration of T cell responses in tuberculosis and augmentation of monocyte effector function againstMycobacterium tuberculosisby natural inhibitors of transforming growth factor β

TGF‐β1 perturbs vascular development and inhibits epithelial differentiation in fetal lung in vivo

Release of transforming growth factor-beta (TGF-β) and fibronectin by alveolar macrophages in airway diseases

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