Cargando…
VEGF-A isoform modulation in an preclinical TNBS model of ulcerative colitis: protective effects of a VEGF164(b) therapy
BACKGROUND: Ulcerative colitis (UC) is the most common form of inflammatory bowel disease in the USA. A key component of UC is the increase in inflammatory angiogenesis of the colon during active disease. This increase is driven to a great extent by the over expression of VEGF-A. Recently, VEGF165(b...
Autores principales: | , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2013
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3848761/ https://www.ncbi.nlm.nih.gov/pubmed/24020796 http://dx.doi.org/10.1186/1479-5876-11-207 |
_version_ | 1782293815775723520 |
---|---|
author | Cromer, Walter E Ganta, Chaitanya V Patel, Mihir Traylor, James Kevil, Christopher G Alexander, J Steven Mathis, J Michael |
author_facet | Cromer, Walter E Ganta, Chaitanya V Patel, Mihir Traylor, James Kevil, Christopher G Alexander, J Steven Mathis, J Michael |
author_sort | Cromer, Walter E |
collection | PubMed |
description | BACKGROUND: Ulcerative colitis (UC) is the most common form of inflammatory bowel disease in the USA. A key component of UC is the increase in inflammatory angiogenesis of the colon during active disease. This increase is driven to a great extent by the over expression of VEGF-A. Recently, VEGF165(b) (VEGF164(b) in mouse), an anti-angiogenic form of VEGF-A was described and its regulation was determined to be disturbed in many pathologies such as cancer and pre-eclampsia. RESULTS: The aims of this study were to examine the role of this inhibitory VEGF by expressing this molecule in a model of intestinal inflammation, and to evaluate its expression as a potential new therapeutic approach for treating UC. A modified model of TNBS colitis was used to determine the effects of rVEGF164(b) expression on colon inflammation. Expansion of the vascular system was assessed by immunhistochemical methods and macro- and microscopic measurements of inflammation in the colon were measured. Leukocyte invasion of the tissue was measured by myeloperoxidase assay and identification and counting of lymphoid follicles. Both angio- and lymphangiogenesis were reduced by expression of rVEGF164(b), which correlated with reduction in both gross and microscopic inflammatory scores. Leukocyte invasion of the tissue was also reduced by rVEGF164(b) expression. CONCLUSIONS: This is the first report using an endogenous inhibitory VEGF-A isoform for therapy in a model of experimental colitis. Inhibitory VEGF molecules play an important role in maintenance of gut homeostasis and may be dysregulated in UC. The results of this study suggest that restoration of rVEGF164(b) expression has anti-inflammatory activity in a TNBS model and warrants further examination as a possible therapeutic for UC. |
format | Online Article Text |
id | pubmed-3848761 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-38487612013-12-04 VEGF-A isoform modulation in an preclinical TNBS model of ulcerative colitis: protective effects of a VEGF164(b) therapy Cromer, Walter E Ganta, Chaitanya V Patel, Mihir Traylor, James Kevil, Christopher G Alexander, J Steven Mathis, J Michael J Transl Med Research BACKGROUND: Ulcerative colitis (UC) is the most common form of inflammatory bowel disease in the USA. A key component of UC is the increase in inflammatory angiogenesis of the colon during active disease. This increase is driven to a great extent by the over expression of VEGF-A. Recently, VEGF165(b) (VEGF164(b) in mouse), an anti-angiogenic form of VEGF-A was described and its regulation was determined to be disturbed in many pathologies such as cancer and pre-eclampsia. RESULTS: The aims of this study were to examine the role of this inhibitory VEGF by expressing this molecule in a model of intestinal inflammation, and to evaluate its expression as a potential new therapeutic approach for treating UC. A modified model of TNBS colitis was used to determine the effects of rVEGF164(b) expression on colon inflammation. Expansion of the vascular system was assessed by immunhistochemical methods and macro- and microscopic measurements of inflammation in the colon were measured. Leukocyte invasion of the tissue was measured by myeloperoxidase assay and identification and counting of lymphoid follicles. Both angio- and lymphangiogenesis were reduced by expression of rVEGF164(b), which correlated with reduction in both gross and microscopic inflammatory scores. Leukocyte invasion of the tissue was also reduced by rVEGF164(b) expression. CONCLUSIONS: This is the first report using an endogenous inhibitory VEGF-A isoform for therapy in a model of experimental colitis. Inhibitory VEGF molecules play an important role in maintenance of gut homeostasis and may be dysregulated in UC. The results of this study suggest that restoration of rVEGF164(b) expression has anti-inflammatory activity in a TNBS model and warrants further examination as a possible therapeutic for UC. BioMed Central 2013-09-11 /pmc/articles/PMC3848761/ /pubmed/24020796 http://dx.doi.org/10.1186/1479-5876-11-207 Text en Copyright © 2013 Cromer et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Cromer, Walter E Ganta, Chaitanya V Patel, Mihir Traylor, James Kevil, Christopher G Alexander, J Steven Mathis, J Michael VEGF-A isoform modulation in an preclinical TNBS model of ulcerative colitis: protective effects of a VEGF164(b) therapy |
title | VEGF-A isoform modulation in an preclinical TNBS model of ulcerative colitis: protective effects of a VEGF164(b) therapy |
title_full | VEGF-A isoform modulation in an preclinical TNBS model of ulcerative colitis: protective effects of a VEGF164(b) therapy |
title_fullStr | VEGF-A isoform modulation in an preclinical TNBS model of ulcerative colitis: protective effects of a VEGF164(b) therapy |
title_full_unstemmed | VEGF-A isoform modulation in an preclinical TNBS model of ulcerative colitis: protective effects of a VEGF164(b) therapy |
title_short | VEGF-A isoform modulation in an preclinical TNBS model of ulcerative colitis: protective effects of a VEGF164(b) therapy |
title_sort | vegf-a isoform modulation in an preclinical tnbs model of ulcerative colitis: protective effects of a vegf164(b) therapy |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3848761/ https://www.ncbi.nlm.nih.gov/pubmed/24020796 http://dx.doi.org/10.1186/1479-5876-11-207 |
work_keys_str_mv | AT cromerwaltere vegfaisoformmodulationinanpreclinicaltnbsmodelofulcerativecolitisprotectiveeffectsofavegf164btherapy AT gantachaitanyav vegfaisoformmodulationinanpreclinicaltnbsmodelofulcerativecolitisprotectiveeffectsofavegf164btherapy AT patelmihir vegfaisoformmodulationinanpreclinicaltnbsmodelofulcerativecolitisprotectiveeffectsofavegf164btherapy AT traylorjames vegfaisoformmodulationinanpreclinicaltnbsmodelofulcerativecolitisprotectiveeffectsofavegf164btherapy AT kevilchristopherg vegfaisoformmodulationinanpreclinicaltnbsmodelofulcerativecolitisprotectiveeffectsofavegf164btherapy AT alexanderjsteven vegfaisoformmodulationinanpreclinicaltnbsmodelofulcerativecolitisprotectiveeffectsofavegf164btherapy AT mathisjmichael vegfaisoformmodulationinanpreclinicaltnbsmodelofulcerativecolitisprotectiveeffectsofavegf164btherapy |