Thymosin ß4 promotes human conjunctival epithelial cell migration

Sosne, Gabriel; Hafeez, S; Greenberry, Albert L.; Kurpakus-Wheater, Michelle

doi:10.1076/ceyr.24.4.268.8414

Cited by 56 publications

(41 citation statements)

References 11 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Interestingly, both the vinculin level and the size of focal adhesions were increased in 3T3 fibroblasts overexpressing Tb-4 (Golla et al, 1997). By contrast, even though the migration of human conjunctival epithelial cells was induced by exogenous Tb-4, their focal contacts to the extracellular matrix were dramatically reduced (Sosne et al, 2002). Our results (Figure 9) are in good agreement with those reported by Golla et al, suggesting that an increased ability to form vinculin-containing focal adhesions of the Tb-4 overexpressers may as well account for their enhanced motilities.…”

Section: Discussionmentioning

confidence: 97%

Overexpression of the thymosin β-4 gene is associated with malignant progression of SW480 colon cancer cells

Wang¹,

Chen²,

Hsiao³

et al. 2003

Oncogene

View full text Add to dashboard Cite

Thymosin b-4 (Tb-4), a small peptide originally isolated from calf thymus, modulates the formation of F-actin microfilaments by sequestering the monomeric G-actin. Recent studies have shown that overexpression of the Tb-4 gene occurs not only in many human carcinomas but also in the highly metastatic melanomas and fibrosarcomas. However, little is known about the specific growth advantages acquired by different tumors from this genetic abnormality. To address the above questions, Tb-4-overexpressing human colon carcinoma (SW480) cells were established by stable transfection and their phenotypic changes were monitored. We found that both the morphology and the cortical actin cytoskeleton of SW480 cells were altered by Tb-4 overexpression. Moreover, both cellular level and that distributed over the intercellular junctions of the E-cadherin were decreased in the Tb-4 overexpressers, which were accompanied by a twofold increase in their saturation densities. Meanwhile, these cells also exhibited an increased ability to form colonies in soft agar. Interestingly, a dramatic increase of growth rate was detected in the Tb-4 overexpressers, which might be attributed to an accelerated proliferation induced by cMyc that was activated by nuclear b-catenin. Finally, a motility increase of these cells was demonstrated by two independent migration assays, which was accompanied by an enhanced focal contact. Taken together, our data suggest that the drastic growth property and motility changes of the SW480 cells overexpressing Tb-4 gene are due mainly to a deregulated cell-cell adhesion arisen from the downregulation of E-cadherin, plus uncontrolled cell proliferation owing to the upregulation of b-catenin, both resulted from a breakdown of actin microfilaments caused by the overexpression of this G-actin sequestering peptide.

show abstract

Section: Discussionmentioning

confidence: 97%

Overexpression of the thymosin β-4 gene is associated with malignant progression of SW480 colon cancer cells

Wang¹,

Chen²,

Hsiao³

et al. 2003

Oncogene

View full text Add to dashboard Cite

show abstract

“…Corneal abrasions are frequently caused by entry of foreign particles such as sand or dust, contact lenses or exposure to ultraviolet radiation and, if untreated, can lead to severe visual impairment. Topical application of Tb4 was shown to promote corneal repair by inducing conjuctival epithelial cell migration, [39] increasing cell-cell and cell-matrix contacts, inhibiting apoptosis [40] and suppressing the activity of matrix metalloproteinases, MMP-2, MMP-9 and MT6-MMP [41]. Interestingly, however, no increased angiogenesis was observed in the eye, even following prolonged treatment with Tb4 [41].…”

Section: Wound Healingmentioning

confidence: 99%

Thymosin β4 and angiogenesis: modes of action and therapeutic potential

Smart¹,

Rossdeutsch²,

Riley³

2007

Angiogenesis

View full text Add to dashboard Cite

show abstract

“…The underlying mechanism may be related to its neurotrophic effect [18][19][20]. Aside from the nervous system, the peptide has activating effects in other systems including enhancement of wound healing [21], stimulation of coreal epithelial cell migration [22], laminin-5 product in vitro [23], and promotion of corneal re-epithelialization and down-regulation of inflammatory mediators [24]. Therefore, we speculate that the neuropromotive effect of Tb4 is mediated by its up-regulation of some viable factor synthesis, which are essential for the survival and functional maintenance of specific populations of neurons.…”

Section: Introductionmentioning

confidence: 99%

The Promotive Effects of Thymosin β4 on Neuronal Survival and Neurite Outgrowth by Upregulating L1 Expression

et al. 2008

View full text Add to dashboard Cite

Thymosin beta(4) (Tbeta4) is a major actin-sequestering peptide widely distributed in mammalian tissues including the nervous system. The presence of this peptide in the nervous system likely plays a role in synaptogensis, axon growth, cell migration, and plastic changes in dendritic spine. However, the effects of Tbeta4 on the survival of neurons and axonal outgrowth have still not been fully understood. So far it is not clear if the effects of Tbeta4 are associated with L1 functions. In the present study, we hypothesized that Tbeta4-induced up-regulation of L1 synthesis could be involved in the survival and axon outgrowth of cultured spinal cord neurons. To test this hypothesis, primarily cultured neurons were prepared from the mouse spinal cord and treated with various concentrations of Tbeta4 ranging from 0.1 to 10 microg/ml. The analysis of L1 mRNA expression and protein synthesis in neurons was then carried out using RT-PCR and western blot assays, respectively. After the addition of Tbeta4 to cultures, cells were then treated with antibodies against distinct domains of L1-Fc. Subsequently, beta-tubulin III and L1 double-labeled indirect immunofluorescence was carried out. Meanwhile, L1 immunofluorescent reactivity was analyzed and compared in cells treated with Tbeta4. Furthermore, the number of beta-tubulin III-positive cells and neurite lengths were measured. We found that Tbeta4 enhanced L1 expression in a dose-dependent manner, and the highest L1 mRNA and protein synthesis in cells increased by more than 2.1- and 2.3-fold in the presence of Tbeta4 at identical concentrations, respectively. Moreover, it also dose dependently enhanced neurite outgrowth and neuronal survival. Compared to conditions without Tbeta4, the length of neurite and neuronal survival increased markedly in presence of 0.5, 1, and 5 microg/ml Tbeta4, respectively, whereas the effects of Tbeta4 were significantly attenuated or inhibited in the process of L1-Fc antibodies treatment. These above results indicate that the promotive effect of Tbeta4 on the survival and neurite outgrowth of cultured spinal cord neurons might be mediated, at least in part via a stimulation of the production of L1 in the neurons.

show abstract

Thymosin ß4 promotes human conjunctival epithelial cell migration

Abstract: Tbeta4 stimulates in vitro conjunctival epithelial cell migration, and results in altered focal adhesion formation and increased extracellular laminin-5 deposition. The increased migration may be correlated with increased production of laminin-5.

Cited by 56 publications

References 11 publications

Overexpression of the thymosin β-4 gene is associated with malignant progression of SW480 colon cancer cells

Overexpression of the thymosin β-4 gene is associated with malignant progression of SW480 colon cancer cells

Thymosin β4 and angiogenesis: modes of action and therapeutic potential

The Promotive Effects of Thymosin β4 on Neuronal Survival and Neurite Outgrowth by Upregulating L1 Expression

Contact Info

Product

Resources

About