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Involvement of insulin-like growth factor-I and insulin-like growth factor binding protein-3 in corneal fibroblasts during corneal wound healing.
Invest Ophthalmol Vis Sci. 2006 Feb; 47(2):591-8.IO

Abstract

PURPOSE

The involvement of downstream messengers of transforming growth factor (TGF)-beta in the differentiation of corneal fibroblasts into myofibroblasts was investigated. The effects of insulin-like growth factor (IGF)-I and insulin-like growth factor binding protein (IGFBP)-3 upregulated by TGF-beta were examined in human corneal fibroblasts, and the possible involvement of IGF axis components in corneal wound healing was assessed in a mouse model.

METHODS

Human corneal fibroblasts were incubated with TGF-beta2 or IGF-I, to investigate IGF-I, IGF-II, IGFBP-3, type I collagen, and alpha-smooth muscle actin (alpha-SMA) mRNA, as well as IGFBP-3 protein expression, during myofibroblast differentiation. DNA synthesis was evaluated with a 5-bromo-2'-deoxyuridine (BrdU) incorporation assay. IGFBP-3 mRNA expression, protein expression, and immunolocalization were investigated in mouse corneas after photorefractive keratectomy (PRK).

RESULTS

TGF-beta2 treatment induced expression of IGF-I and IGFBP-3 mRNA and of IGFBP-3 protein in human corneal fibroblasts. TGF-beta2 and IGF-I both stimulated expression of type I collagen. TGF-beta2 but not IGF-I potently stimulated alpha-SMA mRNA expression. IGF-I potently stimulated basal DNA synthesis, whereas IGFBP-3 inhibited it. IGF-I potently stimulated proliferation of TGF-beta2-activated myofibroblasts without reversing the activated fibrogenic phenotype, whereas IGFBP-3 suppressed IGF-I-induced proliferation of corneal fibroblasts. IGFBP-3 mRNA and protein increased in mouse corneas soon after PRK, when in vivo immunostaining of the corneas showed expression of IGFBP-3 in the deep layer of the corneal stroma.

CONCLUSIONS

These results suggest that during corneal wound healing, TGF-beta stimulates IGF axis components, whereas IGFBP-3 may modulate IGF-I-induced myofibroblast proliferation to suppress corneal mesenchymal overgrowth.

Authors+Show Affiliations

Department of Ophthalmology, Keio University School of Medicine, Tokyo, Japan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

16431955

Citation

Izumi, Kanako, et al. "Involvement of Insulin-like Growth factor-I and Insulin-like Growth Factor Binding Protein-3 in Corneal Fibroblasts During Corneal Wound Healing." Investigative Ophthalmology & Visual Science, vol. 47, no. 2, 2006, pp. 591-8.
Izumi K, Kurosaka D, Iwata T, et al. Involvement of insulin-like growth factor-I and insulin-like growth factor binding protein-3 in corneal fibroblasts during corneal wound healing. Invest Ophthalmol Vis Sci. 2006;47(2):591-8.
Izumi, K., Kurosaka, D., Iwata, T., Oguchi, Y., Tanaka, Y., Mashima, Y., & Tsubota, K. (2006). Involvement of insulin-like growth factor-I and insulin-like growth factor binding protein-3 in corneal fibroblasts during corneal wound healing. Investigative Ophthalmology & Visual Science, 47(2), 591-8.
Izumi K, et al. Involvement of Insulin-like Growth factor-I and Insulin-like Growth Factor Binding Protein-3 in Corneal Fibroblasts During Corneal Wound Healing. Invest Ophthalmol Vis Sci. 2006;47(2):591-8. PubMed PMID: 16431955.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Involvement of insulin-like growth factor-I and insulin-like growth factor binding protein-3 in corneal fibroblasts during corneal wound healing. AU - Izumi,Kanako, AU - Kurosaka,Daijiro, AU - Iwata,Takeshi, AU - Oguchi,Yoshihisa, AU - Tanaka,Yasuhiko, AU - Mashima,Yukihiko, AU - Tsubota,Kazuo, PY - 2006/1/25/pubmed PY - 2006/2/28/medline PY - 2006/1/25/entrez SP - 591 EP - 8 JF - Investigative ophthalmology & visual science JO - Invest Ophthalmol Vis Sci VL - 47 IS - 2 N2 - PURPOSE: The involvement of downstream messengers of transforming growth factor (TGF)-beta in the differentiation of corneal fibroblasts into myofibroblasts was investigated. The effects of insulin-like growth factor (IGF)-I and insulin-like growth factor binding protein (IGFBP)-3 upregulated by TGF-beta were examined in human corneal fibroblasts, and the possible involvement of IGF axis components in corneal wound healing was assessed in a mouse model. METHODS: Human corneal fibroblasts were incubated with TGF-beta2 or IGF-I, to investigate IGF-I, IGF-II, IGFBP-3, type I collagen, and alpha-smooth muscle actin (alpha-SMA) mRNA, as well as IGFBP-3 protein expression, during myofibroblast differentiation. DNA synthesis was evaluated with a 5-bromo-2'-deoxyuridine (BrdU) incorporation assay. IGFBP-3 mRNA expression, protein expression, and immunolocalization were investigated in mouse corneas after photorefractive keratectomy (PRK). RESULTS: TGF-beta2 treatment induced expression of IGF-I and IGFBP-3 mRNA and of IGFBP-3 protein in human corneal fibroblasts. TGF-beta2 and IGF-I both stimulated expression of type I collagen. TGF-beta2 but not IGF-I potently stimulated alpha-SMA mRNA expression. IGF-I potently stimulated basal DNA synthesis, whereas IGFBP-3 inhibited it. IGF-I potently stimulated proliferation of TGF-beta2-activated myofibroblasts without reversing the activated fibrogenic phenotype, whereas IGFBP-3 suppressed IGF-I-induced proliferation of corneal fibroblasts. IGFBP-3 mRNA and protein increased in mouse corneas soon after PRK, when in vivo immunostaining of the corneas showed expression of IGFBP-3 in the deep layer of the corneal stroma. CONCLUSIONS: These results suggest that during corneal wound healing, TGF-beta stimulates IGF axis components, whereas IGFBP-3 may modulate IGF-I-induced myofibroblast proliferation to suppress corneal mesenchymal overgrowth. SN - 0146-0404 UR - https://www.unboundmedicine.com/medline/citation/16431955/Involvement_of_insulin_like_growth_factor_I_and_insulin_like_growth_factor_binding_protein_3_in_corneal_fibroblasts_during_corneal_wound_healing_ L2 - https://iovs.arvojournals.org/article.aspx?doi=10.1167/iovs.05-0097 DB - PRIME DP - Unbound Medicine ER -