Hyperstable EGF-like bleogen derived from cactus accelerates corneal healing in rats
Corneal scarring reduces corneal transparency, compromises vision, and is a major cause of vision loss worldwide. Epidermal growth factor (EGF), which is the prototypic member of the EGF receptor (EGFR) agonists, is present in tears to provide repair and regeneration. Recently, we discovered bleogen...
| Main Authors: | , , |
|---|---|
| Other Authors: | |
| Format: | Journal Article |
| Language: | English |
| Published: |
2023
|
| Subjects: | |
| Online Access: | https://hdl.handle.net/10356/168570 |
| _version_ | 1811682357681324032 |
|---|---|
| author | Loo, Shining Kam, Antony Tam, James P. |
| author2 | School of Biological Sciences |
| author_facet | School of Biological Sciences Loo, Shining Kam, Antony Tam, James P. |
| author_sort | Loo, Shining |
| collection | NTU |
| description | Corneal scarring reduces corneal transparency, compromises vision, and is a major cause of vision loss worldwide. Epidermal growth factor (EGF), which is the prototypic member of the EGF receptor (EGFR) agonists, is present in tears to provide repair and regeneration. Recently, we discovered bleogen pB1 in the cactus plant Pereskia bleo and showed that it is a non-canonical and hyperstable EGFR agonist with EGF-like wound healing properties for diabetic rats. Here, we apply bleogen pB1 to accelerate corneal wound healing in rats. To assess the corneal healing effects of bleogen pB1, we induced an acute alkali burn to the right eye of male Wistar rats. After five consecutive ophthalmic applications, fluorescein staining and opacity scores of the bleogen pB1-treated, and the positive control EGF-treated groups improved significantly compared to the saline control group. Immunohistochemical analyses revealed that infiltrated CD68+ macrophages and the expression of the myofibroblast marker alpha smooth muscle actin (α-SMA) were significantly decreased in the bleogen pB1- and the EGF-treated groups. By employing a differential gene expression analysis of bleogen pB1- and EGF-treated keratinocytes through RNA-seq, we demonstrated that bleogen pB1 or EGF treatments can affect the expression of genes associated with inflammatory responses and extracellular matrix remodeling. Taken together, our results indicate that the plant-derived EGFR agonist bleogen pB1 can produce similar effects to those of EGF in accelerating corneal wound healing as well as in reducing persistent inflammation and myofibroblast accumulation in the cornea. |
| first_indexed | 2024-10-01T03:55:33Z |
| format | Journal Article |
| id | ntu-10356/168570 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2024-10-01T03:55:33Z |
| publishDate | 2023 |
| record_format | dspace |
| spelling | ntu-10356/1685702023-06-12T15:31:57Z Hyperstable EGF-like bleogen derived from cactus accelerates corneal healing in rats Loo, Shining Kam, Antony Tam, James P. School of Biological Sciences Science::Biological sciences Bleogen Cactus Corneal scarring reduces corneal transparency, compromises vision, and is a major cause of vision loss worldwide. Epidermal growth factor (EGF), which is the prototypic member of the EGF receptor (EGFR) agonists, is present in tears to provide repair and regeneration. Recently, we discovered bleogen pB1 in the cactus plant Pereskia bleo and showed that it is a non-canonical and hyperstable EGFR agonist with EGF-like wound healing properties for diabetic rats. Here, we apply bleogen pB1 to accelerate corneal wound healing in rats. To assess the corneal healing effects of bleogen pB1, we induced an acute alkali burn to the right eye of male Wistar rats. After five consecutive ophthalmic applications, fluorescein staining and opacity scores of the bleogen pB1-treated, and the positive control EGF-treated groups improved significantly compared to the saline control group. Immunohistochemical analyses revealed that infiltrated CD68+ macrophages and the expression of the myofibroblast marker alpha smooth muscle actin (α-SMA) were significantly decreased in the bleogen pB1- and the EGF-treated groups. By employing a differential gene expression analysis of bleogen pB1- and EGF-treated keratinocytes through RNA-seq, we demonstrated that bleogen pB1 or EGF treatments can affect the expression of genes associated with inflammatory responses and extracellular matrix remodeling. Taken together, our results indicate that the plant-derived EGFR agonist bleogen pB1 can produce similar effects to those of EGF in accelerating corneal wound healing as well as in reducing persistent inflammation and myofibroblast accumulation in the cornea. Ministry of Education (MOE) Nanyang Technological University Published version This research was supported in part by a Competitive Research Grant by the Nanyang Technological University Internal Funding - Synzyme and Natural Products (SYNC) and by an AcRF Tier three funding (MOE2016-T3-1-003). SL and AK are recipients of the Mistletoe Research Fellowship. 2023-06-06T01:50:47Z 2023-06-06T01:50:47Z 2022 Journal Article Loo, S., Kam, A. & Tam, J. P. (2022). Hyperstable EGF-like bleogen derived from cactus accelerates corneal healing in rats. Frontiers in Pharmacology, 13, 942168-. https://dx.doi.org/10.3389/fphar.2022.942168 1663-9812 https://hdl.handle.net/10356/168570 10.3389/fphar.2022.942168 36052138 2-s2.0-85137053385 13 942168 en MOE2016-T3-1-003 Frontiers in Pharmacology © 2022 Loo, Kam and Tam. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. application/pdf |
| spellingShingle | Science::Biological sciences Bleogen Cactus Loo, Shining Kam, Antony Tam, James P. Hyperstable EGF-like bleogen derived from cactus accelerates corneal healing in rats |
| title | Hyperstable EGF-like bleogen derived from cactus accelerates corneal healing in rats |
| title_full | Hyperstable EGF-like bleogen derived from cactus accelerates corneal healing in rats |
| title_fullStr | Hyperstable EGF-like bleogen derived from cactus accelerates corneal healing in rats |
| title_full_unstemmed | Hyperstable EGF-like bleogen derived from cactus accelerates corneal healing in rats |
| title_short | Hyperstable EGF-like bleogen derived from cactus accelerates corneal healing in rats |
| title_sort | hyperstable egf like bleogen derived from cactus accelerates corneal healing in rats |
| topic | Science::Biological sciences Bleogen Cactus |
| url | https://hdl.handle.net/10356/168570 |
| work_keys_str_mv | AT looshining hyperstableegflikebleogenderivedfromcactusacceleratescornealhealinginrats AT kamantony hyperstableegflikebleogenderivedfromcactusacceleratescornealhealinginrats AT tamjamesp hyperstableegflikebleogenderivedfromcactusacceleratescornealhealinginrats |