Transforming growth factor‐bβ<sub>1</sub>: its anti‐inflammatory and pro‐fibrotic effects

Ling, Eleanor M.; Robinson, Douglas S.

doi:10.1046/j.1365-2222.2002.01287.x

Cited by 64 publications

(49 citation statements)

References 49 publications

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“…This is also seen in oncogenesis, where TGF-␤ 1 can exert potent growth inhibitory effects on tumor cells while enhancing tumor cell migration and invasion. Particularly relevant to the present study are the studies that demonstrate that, in the proper setting, TGF-␤ 1 is essential for wound healing, stimulates matrix molecule deposition and angiogenesis, and is an essential mediator of the pathologic scarring in fibrotic disorders (7,17,(28)(29)(30)(31). On the other hand, TGF-␤ 1 can induce tissue injury (32) and cellular apoptosis, decrease epithelialization, and inhibit wound healing (33)(34)(35)(36).…”

Section: Tgf-␤ 1 Effector Functionsmentioning

confidence: 86%

Transgenic Modeling of Transforming Growth Factor- 1: Role of Apoptosis in Fibrosis and Alveolar Remodeling

Lee

Kang²,

Homer³

et al. 2006

Proceedings of the American Thoracic Society

104

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Inflammation and tissue remodeling with pathologic fibrosis are common consequences of Th2 responses in the lung and other organs. Interleukin (IL)-13 and transforming growth factor-␤1 (TGF-␤ 1 ) are frequently coexpressed in these responses and are believed to play important roles in the pathogenesis of Th2-induced pathologies. To shed light on the mechanisms of these responses, overexpression transgenic approaches were used to selectively target each of these cytokines to the murine lung. IL-13 proved to be a potent stimulator of eosinophilic inflammation, mucus metaplasia, tissue fibrosis, and alveolar remodeling. CC chemokines, specific chemokine receptors (CCR2, CCR1), adenosine metabolism, vascular endothelial growth factor, and IL-11 contributed to the genesis of these responses. IL-13 also induced tissue fibrosis, at least in part, via its ability to induce and activate TGF-␤ 1 . In the TGF-␤ 1 transgenic mouse, epithelial apoptosis preceded the onset of tissue fibrosis and alveolar remodeling. In addition, chemical (Z-VAD-fmk) and genetic (null mutations of early growth response gene 1) interventions blocked apoptosis and ameliorated TGF-␤ 1 -induced fibrosis and alveolar restructuring. These studies define an IL-13-TGF-␤ 1 pathway of tissue remodeling that regulates inflammation, mucus metaplasia, apoptosis, vascular responses, and fibrosis in the lung. They also highlight the intimate relationship between apoptosis and fibrosis induced by TGF-␤ 1 . By defining the complexities of this pathway, these studies highlight sites at which therapies can be directed to control these important responses.

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Section: Tgf-␤ 1 Effector Functionsmentioning

confidence: 86%

Transgenic Modeling of Transforming Growth Factor- 1: Role of Apoptosis in Fibrosis and Alveolar Remodeling

Lee

Kang²,

Homer³

et al. 2006

Proceedings of the American Thoracic Society

104

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“…of cyclin-dependent kinases CDK1 and CDK2, which blocks the transition from G 1 phase to S phase or from G 2 phase to mitosis after DNA damage, enabling the repair of damaged DNA (18). p21 is a negative regulator of lung fibrosis induced by TGF-β1 (17), which promotes lung inflammation and fibrosis in patients with various diseases, including chronic obstructive pulmonary disease, idiopathic pulmonary fibrosis, and lung cancer (47). Our results show that p21 silencing in lung tumor cells influences collagen cross-linking in the tumor stroma through the upregulation of LH2 expression.…”

Section: Discussionmentioning

confidence: 99%

Lysyl hydroxylase 2 induces a collagen cross-link switch in tumor stroma

Chen¹,

Terajima²,

Yang³

et al. 2015

J. Clin. Invest.

145

188

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“…1). A number of studies demonstrate that, in the proper setting, TGF-b 1 is essential for wound healing, stimulates matrix molecule deposition and angiogenesis, and is an essential mediator of the pathologic scarring in fibrotic disorders (2)(3)(4)(5)(6). On the other hand, TGF-b 1 can also induce tissue injury and cellular apoptosis, decrease epithelialization, and inhibit wound healing (7)(8)(9)(10)(11)(12).…”

mentioning

confidence: 99%

P21 Regulates TGF-β₁–Induced Pulmonary Responses via a TNF-α–Signaling Pathway

Yamasaki¹,

Kang²,

Homer³

et al. 2008

Am J Respir Cell Mol Biol

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Transforming growth factor (TGF)-b 1 is an essential regulatory cytokine that has been implicated in the pathogenesis of diverse facets of the injury and repair responses in the lung. The types of responses that it elicits can be appreciated in studies from our laboratory that demonstrated that the transgenic (Tg) overexpression of TGF-b 1 in the murine lung causes epithelial apoptosis followed by fibrosis, inflammation, and parenchymal destruction. Because a cyclin-dependent kinase inhibitor, p21, is a key regulator of apoptosis, we hypothesized that p21 plays an important role in the pathogenesis of TGF-b 1 -induced tissue responses. To test this hypothesis we evaluated the effect of TGF-b 1 on the expression of p21 in the murine lung. We also characterized the effects of transgenic TGFb 1 in mice with wild-type and null mutant p21 loci. These studies demonstrate that TGF-b 1 is a potent stimulator of p21 expression in the epithelial cells and macrophages in the murine lung. They also demonstrate that TGF-b 1 -induced lung inflammation, fibrosis, myofibroblast accumulation, and alveolar destruction are augmented in the absence of p21, and that these alterations are associated with exaggerated levels of apoptosis and caspase-3 activation. Finally, our studies further demonstrated that TGF-b 1 induces p21 via a TNF-asignaling pathway and that p21 is a negative modulator of TGF-b 1 -induced TNF-a expression. Collectively, our studies demonstrate that p21 regulates TGF-b 1 -induced apoptosis, inflammation, fibrosis, and alveolar remodeling by interacting with TNF-a-signaling pathways.

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Transforming growth factor‐bβ₁: its anti‐inflammatory and pro‐fibrotic effects

Cited by 64 publications

References 49 publications

Transgenic Modeling of Transforming Growth Factor- 1: Role of Apoptosis in Fibrosis and Alveolar Remodeling

Transgenic Modeling of Transforming Growth Factor- 1: Role of Apoptosis in Fibrosis and Alveolar Remodeling

Lysyl hydroxylase 2 induces a collagen cross-link switch in tumor stroma

P21 Regulates TGF-β₁–Induced Pulmonary Responses via a TNF-α–Signaling Pathway

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Transforming growth factor‐bβ1: its anti‐inflammatory and pro‐fibrotic effects

Cited by 64 publications

References 49 publications

Transgenic Modeling of Transforming Growth Factor- 1: Role of Apoptosis in Fibrosis and Alveolar Remodeling

Transgenic Modeling of Transforming Growth Factor- 1: Role of Apoptosis in Fibrosis and Alveolar Remodeling

Lysyl hydroxylase 2 induces a collagen cross-link switch in tumor stroma

P21 Regulates TGF-β1–Induced Pulmonary Responses via a TNF-α–Signaling Pathway

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Product

Resources

About

Transforming growth factor‐bβ₁: its anti‐inflammatory and pro‐fibrotic effects

P21 Regulates TGF-β₁–Induced Pulmonary Responses via a TNF-α–Signaling Pathway