Thrombospondin-1 accelerates wound healing of corneal epithelia

Uno, Koichi; Hayashi, Hideyuki; Uchida, Hiroko; Yamauchi, Yasushi; Kuroki, Masahide; Oshima, Kenji

doi:10.1016/j.bbrc.2004.01.146

Cited by 49 publications

(58 citation statements)

References 18 publications

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“…In human epithelium-derived cancer cells, EGF increases TSP1 expression (21). TSP1 expression is increased during tissue repair and wound healing (7,64) where it accelerates re-epithelialization (8). In a murine model of corneal abrasion, exogenous TSP1 stimulated epithelialization, whereas anti-TSP1 antibodies inhibited it (8).…”

Section: Discussionmentioning

confidence: 99%

“…In other experiments, A431 cells were exposed to a fixed concentration of TSP1 (30 g/ml or 214 nM) for increasing times, after which the cells were lysed and the lysates processed for phospho-EGFR Tyr-992 (B) and Tyr-1173 (C) immunoblotting. To indicate protein loading and transfer, blots were stripped and reprobed with anti-␤-tubulin antibodies (A, lanes [5][6][7][8]. IB, immunoblot; IB*, immunoblot after stripping.…”

Section: Pattern Of Egfr Tyrosine Autophosphorylation In Response To mentioning

confidence: 99%

“…Much of our understanding of TSP1 biology has been established in these cell systems. TSP1 is also expressed in epithelia, is abundant in the basement membranes underlying these cells (17), and participates in epithelial cell responses, including re-epithelialization during wound healing (8), bronchial epithelial cell morphogenesis and development (19), and migration of epithelium-derived tumor cells (20). In human epithelium-derived cancer cells, EGF increases TSP1 expression (21).…”

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confidence: 99%

“…TSP1 recognizes multiple cell surface receptors coupled to specific signaling pathways that evoke distinct, and sometimes opposing, biological responses (5,7,8). The NH 2 -terminal globular domain recognizes heparan sulfate proteoglycans (6), low density lipoprotein receptor-related protein 1 (9), sulfated glycolipids (10), calreticulin (9), and integrins (11).…”

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confidence: 99%

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Epidermal Growth Factor-like Repeats of Thrombospondins Activate Phospholipase Cγ and Increase Epithelial Cell Migration through Indirect Epidermal Growth Factor Receptor Activation

Liu

Garg

Yang

et al. 2009

Journal of Biological Chemistry

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Thrombospondin (TSP) 1 is a trimeric multidomain protein that contains motifs that recognize distinct host cell receptors coupled to multiple signaling pathways. Selected TSP1-induced cellular responses are tyrosine kinasedependent, and TSP1 contains epidermal growth factor (EGF)-like repeats. Specific receptor interactions or functions for the EGF-like repeats have not been identified. We asked whether one or more biological responses to TSP1 might be explained through EGF receptor (EGFR) activation. In A431 cells, TSP1 increased autophosphorylation of Tyr-1068 of EGFR in a dose-and time-dependent manner. The ability of TSP1 to activate EGFR was replicated by the tandem EGF-like repeats as a recombinant protein. The three EGFlike repeats alone produced a high level of Tyr-1068 phosphorylation. EGF-like repeats from TSP2 and TSP4 also activated EGFR. Tyr-1068 phosphorylation was less when individual EGF-like repeats were tested or flanking sequences were added to the three EGF-like repeats. TSP1 and its EGF-like repeats also increased phosphorylation of EGFR Tyr-845, Tyr-992, Tyr-1045, Tyr-1086, and Tyr-1173, activated phospholipase C␥, and increased cell migration. No evidence was found for binding of the EGF-like repeats to EGFR. Instead, EGFR activation in response to TSP1 or its EGF-like repeats required matrix metalloprotease activity, including activity of matrix metalloprotease 9. Access to the ligand-binding portion of the EGFR ectodomain was also required. These findings suggest release of an endogenous EGFR ligand in response to ligation of a second unknown receptor by the TSPs.

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Section: Discussionmentioning

confidence: 99%

Section: Pattern Of Egfr Tyrosine Autophosphorylation In Response To mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Epidermal Growth Factor-like Repeats of Thrombospondins Activate Phospholipase Cγ and Increase Epithelial Cell Migration through Indirect Epidermal Growth Factor Receptor Activation

Liu

Garg

Yang

et al. 2009

Journal of Biological Chemistry

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“…The 13 genes induced by the activin-MEKK1 pathway were grouped into four categories (Table 1) and detailed analyses revealed a functional relationship for 11 of them in the regulation of ECM homeostasis, resulting in increased expression of ECM components and the induction of proteases and their inhibitors that might further regulate ECM degradation (Albo et al, 1999;Chen et al, 2001a;Dallas et al, 2002). Interestingly, all these genes are known to be highly induced by tissue injury, and their expression is implicated in cell motility and wound healing (Chiquet-Ehrismann, 1995;Li et al, 2000;Engers et al, 2001;Uno et al, 2004).…”

Section: The Mekk1 Pathway Leads To Ecm Remodeling Of Gene Expressionmentioning

confidence: 99%

A Role for the Mitogen-activated Protein Kinase Kinase Kinase 1 in Epithelial Wound Healing

Deng

Chen

Takatori

et al. 2006

MBoC

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The mitogen-activated protein kinase kinase (MEK) kinase 1 (MEKK1) mediates activin B signals required for eyelid epithelium morphogenesis during mouse fetal development. The present study investigates the role of MEKK1 in epithelial wound healing, another activin-regulated biological process. In a skin wound model, injury markedly stimulates MEKK1 expression and activity, which are in turn required for the expression of genes involved in extracellular matrix (ECM) homeostasis. MEKK1 ablation or down-regulation by interfering RNA significantly delays skin wound closure and impairs activation of Jun NH 2 -terminal kinases, induction of plasminogen activator inhibitor (PAI)-1, and restoration of cell-cell junctions of the wounded epidermis. Conversely, expression of wild-type MEKK1 accelerates reepithelialization of full-thickness skin and corneal debridement wounds by mechanisms involving epithelial cell migration, a cell function that is partially abolished by neutralizing antibodies for PAI-1 and metalloproteinase III. Our data suggest that MEKK1 transmits wound signals, leading to the transcriptional activation of genes involved in ECM homeostasis, epithelial cell migration, and wound reepithelialization.

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Secretome Analysis of Human Nasal Fibroblast Identifies Proteins That Promote Wound Healing

Man

Idrus

Ibrahim

et al. 2023

Advances in Experimental Medicine and Biology

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Thrombospondin-1 accelerates wound healing of corneal epithelia

Cited by 49 publications

References 18 publications

Epidermal Growth Factor-like Repeats of Thrombospondins Activate Phospholipase Cγ and Increase Epithelial Cell Migration through Indirect Epidermal Growth Factor Receptor Activation

Epidermal Growth Factor-like Repeats of Thrombospondins Activate Phospholipase Cγ and Increase Epithelial Cell Migration through Indirect Epidermal Growth Factor Receptor Activation

A Role for the Mitogen-activated Protein Kinase Kinase Kinase 1 in Epithelial Wound Healing

Secretome Analysis of Human Nasal Fibroblast Identifies Proteins That Promote Wound Healing

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