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Use of galectin-7 to promote the re-epithelialization of wounds

a technology of reepithelialization and galectin, which is applied in the direction of dermatological disorders, drug compositions, peptide/protein ingredients, etc., can solve the problems of limited success in accelerating wound healing with pharmaceutical agents, persistent corneal epithelial defects carry a high risk of corneal perforation and ulceration, and wound healing disorders constitute serious medical problems. , to achieve the effect of promoting reepithelialization of wounds, promoting reepi

Inactive Publication Date: 2009-10-29
PANJWANI NOORJAHAN +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Disorders of wound healing constitute a serious medical problem for several different organ systems including the skin, gastrointestinal tract, and cornea.
Persistent corneal epithelial defects carry a high risk of corneal perforation and ulceration (Macaluso et al., supra).
Despite the need for more rapid healing of wounds, to date there has been only limited success in accelerating wound healing with pharmaceutical agents.
92:77, 1985) does not always result in successful long-term management.
26:92, 1985), enhances epithelial wound healing but does not prevent recurrent erosion and secondary breakdown of the corneal epithelial surface.

Method used

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  • Use of galectin-7 to promote the re-epithelialization of wounds
  • Use of galectin-7 to promote the re-epithelialization of wounds
  • Use of galectin-7 to promote the re-epithelialization of wounds

Examples

Experimental program
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Effect test

example 1

Up-Regulation of Galectin-3 in Migrating Corneal Epithelium Following Injury

[0078]To determine whether the expression level of galectin-3 is altered in the epithelium of healing corneas following injury, mice corneas with 2 mm excimer laser ablations and abrasion wounds, were allowed to partially heal in vivo and were then processed for immunostaining with rat anti-human galectin-3 mAb M3 / 38 (American Type Culture Collection, Rockville, Md.). Corneal epithelium is a prototype-stratified squamous epithelium. In mouse, it constitutes 20-25% of total corneal thickness and is composed of 5 to 6 layers of cells. Posterior to the epithelial basement membrane is corneal stroma, which in mouse represents 70-80% of the total corneal thickness. Abrasion wounds remove epithelium leaving the corneal stroma intact. In contrast, excimer laser treatment, which is commonly used for correction of myopia, removes epithelium as well as anterior corneal stroma.

[0079]Swiss Webster mice (Taconic Laborato...

example 2

Corneal Epithelial Wound Closure in Wild Type and Galectin-3 Deficient Mice

[0084]To determine whether the re-epithelialization of corneal wounds is impaired in galectin-3 deficient mice, four different models of corneal wound healing were used. Galectin-3 deficient mice (gal-3− / −) were generated by targeted interruption of the galectin-3 gene as described in Hsu et al., Am. J. Pathol. 156:1073, 2000. Specifically, the region coding for the CRD was interrupted with a neomycin resistant gene. This involved substituting a 0.5 kb intron 4-exon 5 segment with the antibiotic resistant gene (neo). That the galectin-3 gene has been inactivated was confirmed by Southern blot as well as Western blot analysis.

[0085]Briefly, corneas with excimer laser ablations (as described in Example 1) or alkali-burn wounds were allowed to partially heal in vivo or in vitro (as described in Example 1). For alkali injury, 2 mm filter discs (Whatman 50, Whatman International, Maidstone, UK) were prepared using...

example 3

Gene Expression Patterns in Migrating Corneal Epithelium of Galectin-3 Deficient Mice Following Injury

[0086]In an attempt to understand why the re-epithelialization of corneal epithelial wounds is perturbed in gal-3− / − mice, gene expression patterns of healing gal-3+ / + and gal-3− / − corneas were compared using cDNA microarrays and the results were further confirmed by semiquantitative RT-PCR.

[0087]Transepithelial excimer laser ablations (2 mm diameter) were produced on the right eye of 30 gal+ / + and 30 gal− / − mice as described in Example 1. Corneas were allowed to partially heal in vivo for 20 to 24 hours. At the end of the healing period, animals were sacrificed and the corneas were excised and immediately placed in liquid nitrogen and shipped to Clontech Laboratories, Palo Alto, Calif. for analysis of gene expression using SMART™ cDNA technology. Briefly, total RNA was isolated using the reagents provided in the ATLAS™ Pure Total RNA Labeling System. Yield of RNA from the 30 gal-3+...

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Abstract

Methods for the therapeutic treatment of epithelial wounds in mammals comprising administering to a mammal afflicted with an epithelial wound a therapeutically effective amount of a galectin-3 protein and / or a galectin-7 protein are provided. Pharmaceutical compositions comprising a pharmaceutically suitable carrier or diluent and as an active agent a galectin-3 protein and / or a galectin-7 protein are also provided.

Description

RELATED APPLICATIONS[0001]The present application claims priority to provisional application U.S. Ser. No. 60 / 286,903, filed Apr. 27, 2001 which is incorporated herein by reference in its entirety.GOVERNMENT FUNDING[0002]This invention was made with Government support under grant number EY-07088 from the National Institutes of Health. Accordingly, the government may have certain rights in this invention.BACKGROUND OF THE INVENTION[0003]The repair of wounds in mammalian tissue (e.g., epithelial defects, lesions, or erosions caused by disease, accidental injury, surgical procedure, etc.) involves an orderly, controlled cellular response. Three phases have been described in normal wound healing: acute inflammatory phase, extracellular matrix and collagen synthesis, and remodeling (Wound Repair by Peacock, W.B. Saunders, Philadelphia, Pa., 1984). The sequence of the healing process is initiated during an acute inflammatory phase with the deposition of provisional tissue. This is followe...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): A61K38/17
CPCA61K38/1709
Inventor PANJWANI, NOORJAHANCAO, ZHIYI
Owner PANJWANI NOORJAHAN
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