Lens-Specific Expression of TGF-β Induces Anterior Subcapsular Cataract Formation in the Absence of Smad3

Banh, Alice; Deschamps, Paula; Gauldie, Jack; Overbeek, Paul A.; Sivak, J. G.; West‐Mays, Judith A.

doi:10.1167/iovs.05-1208

Cited by 58 publications

(77 citation statements)

References 58 publications

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“…That Smad2 phosphorylation is detected in Arf-expressing cells in the embryo suggests but does not prove it to be the crucial Smad in vivo. Its candidacy is strengthened by the fact that Smad3 -/-mice, which are viable, appear to have normal eyes (Banh et al, 2006;Zhu et al, 1998). Formally evaluating the role of Smad2 may require its knockout in cells destined to express the Arf promoter because Smad2 -/-mice suffer early embryonic lethality (Nomura and Li, 1998;Weinstein et al, 1998).…”

Section: Discussionmentioning

confidence: 99%

Expression of theArftumor suppressor gene is controlled by Tgfβ2 during development

et al. 2009

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The Arf tumor suppressor (also known as Cdkn2a) acts as an oncogene sensor induced by 'abnormal' mitogenic signals in incipient cancer cells. It also plays a crucial role in embryonic development: newborn mice lacking Arf are blind due to a pathological process resembling severe persistent hyperplastic primary vitreous (PHPV), a human eye disease. The cell-intrinsic mechanism implied in the oncogene sensor model seems unlikely to explain Arf regulation during embryo development. Instead, transforming growth factor β2 (Tgfβ2) might control Arf expression, as we show that mice lacking Tgfβ2 have primary vitreous hyperplasia similar to Arf -/-mice. Arf expression can be coupled to extracellular cues in normal cells and suggest a new mechanism for Arf control in tumor cells.

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Section: Discussionmentioning

confidence: 99%

Expression of theArftumor suppressor gene is controlled by Tgfβ2 during development

et al. 2009

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“…TGFb can terminate the induction of its own target genes by recruiting Smad7, which negatively regulates signalling strength and duration, through formation of a negative-feedback loop [73]. A body of evidence has been obtained regarding the involvement of the classical TGFb/Smad signalling pathway in the pathogenesis of fibrotic disorders of the lens [6,13,14,19]. Work by Saika et al [19] has shown Smad3 and Smad4 to be present in cell nuclei of post-operative human lenses and in injury-induced epithelial to mesenchymal transition (EMT) murine lenses [74], therefore implicating activation by TGFb following trauma.…”

Section: Tgfb: the Orchestrator Of Fibrosismentioning

confidence: 99%

The lens as a model for fibrotic disease

Eldred

Dawes

Wormstone

2011

Phil. Trans. R. Soc. B

103

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Fibrosis affects multiple organs and is associated with hyperproliferation, cell transdifferentiation, matrix modification and contraction. It is therefore essential to discover the key drivers of fibrotic events, which in turn will facilitate the development of appropriate therapeutic strategies. The lens is an elegant experimental model to study the processes that give rise to fibrosis. The molecular and cellular organization of the lens is well defined and consequently modifications associated with fibrosis can be clearly assessed. Moreover, the avascular and non-innervated properties of the lens allow effective in vitro studies to be employed that complement in vivo systems and relate to clinical data. Using the lens as a model for fibrosis has direct relevance to millions affected by lens disorders, but also serves as a valuable experimental tool to understand fibrosis per se.

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“…The biological function of TGF-β is mediated via the conduction of types I (RI) and II (RII) transmembrane receptors (7). TGF-β is present in almost all cells; therefore, it can influence the physiological function of the majority of tissues correspondingly (8). In vitro, TGF-β Tocotrienol alleviates inflammation and oxidative stress in a rat model of spinal cord injury via suppression of transforming growth factor-β is a potent agent for astrocyte chemotaxis, which can result in the hypertrophy of astrocytes and upregulation of the synthesis of fibronectin and collagen IV (8).…”

Section: Introductionmentioning

confidence: 99%

“…TGF-β is present in almost all cells; therefore, it can influence the physiological function of the majority of tissues correspondingly (8). In vitro, TGF-β Tocotrienol alleviates inflammation and oxidative stress in a rat model of spinal cord injury via suppression of transforming growth factor-β is a potent agent for astrocyte chemotaxis, which can result in the hypertrophy of astrocytes and upregulation of the synthesis of fibronectin and collagen IV (8). Tocotrienols are isomers of vitamin E, located primarily in plants, with antioxidative (9), anti-tumor (10) and neuroprotective functions (11).…”

Section: Introductionmentioning

confidence: 99%

Tocotrienol alleviates inflammation and oxidative stress in a rat model of spinal cord injury via suppression of transforming growth factor-β

Xun

Mamat

Guo

et al. 2017

Experimental and Therapeutic Medicine

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Abstract. In recent years accumulating evidence has indicated that tocotrienol exhibits an oxidation resistance function, decreased cholesterol function, inhibits cancer function and has unique physiological functions, including anti-inflammatory, anti-apoptotic and anti-oxidative properties. The present study investigated the effect of tocotrienols on spinal cord injury (SCI) by evaluating oxidative stress, inflammation and inducible nitric oxide synthase (iNOS) in rats. A rat model of SCI was induced by operation. SCI rats were treated with 120 mg/kg/day tocotrienol once a day for eight consecutive weeks. Functional recovery following SCI was measured by using the Basso Beattie Bresnahan (BBB) locomotor rating scale. Then the volume of spinal cord contusions was measured following induction of SCI in the rats. In SCI rats, serum malondialdehyde, superoxide dismutase, catalase, glutathione peroxidase, nuclear factor-κB p65 unit, tumor necrosis factor-α, interleukin (IL)-1β and IL-6 levels were analyzed using respective commercial immunoassay kits. Firstly, iNOS, transforming growth factor (TGF)-β, collagen type IV and fibronectin protein expression levels, in addition to iNOS activity and plasma nitric oxide (NO) production in SCI rats was analyzed using western blot analysis, commercial kits and Griess reagent, respectively. Tocotrienol treatment elevated BBB scores and contused volume in the SCI rats. Tocotrienol protected against SCI with reduced oxidative stress and inflammation, and inhibited iNOS protein expression iNOS activity and plasma NO production in rats. In addition, treatment with tocotrienols suppressed TGF-β, collagen type IV and fibronectin protein expression levels in SCI rats. These results suggest that tocotrienols protect SCI, and suppress oxidative stress, inflammation and iNOS in this model of SCI through TGF-β, collagen type IV and fibronectin signaling pathways.

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Lens-Specific Expression of TGF-β Induces Anterior Subcapsular Cataract Formation in the Absence of Smad3

Abstract: Lens-specific expression of TGF-beta1 induced ASC formation in the absence of the Smad3 signaling mediator, suggests that alternative TGF-beta-signaling pathways participate in this ocular fibrotic model.

Cited by 58 publications

References 58 publications

Expression of theArftumor suppressor gene is controlled by Tgfβ2 during development

Expression of theArftumor suppressor gene is controlled by Tgfβ2 during development

The lens as a model for fibrotic disease

Tocotrienol alleviates inflammation and oxidative stress in a rat model of spinal cord injury via suppression of transforming growth factor-β

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