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AdhMMP8 Vector Administration in Muscle: An Alternate Strategy to Regress Hepatic Fibrosis
The development of several vaccines against the SARS-CoV2 virus and their application in millions of people have shown efficacy and safety in the transfer of genes to muscle turning this tissue into a protein-producing factory. Established advanced liver fibrosis, is characterized by replacement of...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10486800/ https://www.ncbi.nlm.nih.gov/pubmed/37681859 http://dx.doi.org/10.3390/cells12172127 |
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author | García-Bañuelos, Jesús Oceguera-Contreras, Edén Sandoval-Rodríguez, Ana Bastidas-Ramírez, Blanca Estela Lucano-Landeros, Silvia Gordillo-Bastidas, Daniela Gómez-Meda, Belinda C. Santos, Arturo Cerda-Reyes, Eira Armendariz-Borunda, Juan |
author_facet | García-Bañuelos, Jesús Oceguera-Contreras, Edén Sandoval-Rodríguez, Ana Bastidas-Ramírez, Blanca Estela Lucano-Landeros, Silvia Gordillo-Bastidas, Daniela Gómez-Meda, Belinda C. Santos, Arturo Cerda-Reyes, Eira Armendariz-Borunda, Juan |
author_sort | García-Bañuelos, Jesús |
collection | PubMed |
description | The development of several vaccines against the SARS-CoV2 virus and their application in millions of people have shown efficacy and safety in the transfer of genes to muscle turning this tissue into a protein-producing factory. Established advanced liver fibrosis, is characterized by replacement of hepatic parenchyma by tissue scar, mostly collagen type I, with increased profibrogenic and proinflammatory molecules gene expression. Matrix metalloproteinase 8 (MMP-8) is an interstitial collagen-degrading proenzyme acting preferentially on collagen type I when activated. This study was carried out to elucidate the effect of an intramuscularly delivered adenoviral vector containing proMMP-8 gene cDNA (AdhMMP8) in male Wistar rats with experimental advanced liver fibrosis induced by thioacetamide. Therapeutic effects were monitored after 1, 2, or 3 weeks of a single dose (3 × 10(11) vp/kg) of AdhMMP8. Circulating and liver concentration of MMP-8 protein remained constant; hepatic fibrosis decreased up to 48%; proinflammatory and profibrogenic genes expression diminished: TNF-α 2.28-fold, IL-1 1.95-fold, Col 1A1 4-fold, TGF-β1 3-fold and CTGF 2-fold; and antifibrogenic genes expression raised, MMP-9 2.8-fold and MMP-1 10-fold. Our data proposes that the administration of AdhMMP8 in muscle is safe and effective in achieving liver fibrosis regression at a comparable extent as when the adenoviral vector is delivered systemically to reach the liver, using a minimally invasive procedure. |
format | Online Article Text |
id | pubmed-10486800 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-104868002023-09-09 AdhMMP8 Vector Administration in Muscle: An Alternate Strategy to Regress Hepatic Fibrosis García-Bañuelos, Jesús Oceguera-Contreras, Edén Sandoval-Rodríguez, Ana Bastidas-Ramírez, Blanca Estela Lucano-Landeros, Silvia Gordillo-Bastidas, Daniela Gómez-Meda, Belinda C. Santos, Arturo Cerda-Reyes, Eira Armendariz-Borunda, Juan Cells Article The development of several vaccines against the SARS-CoV2 virus and their application in millions of people have shown efficacy and safety in the transfer of genes to muscle turning this tissue into a protein-producing factory. Established advanced liver fibrosis, is characterized by replacement of hepatic parenchyma by tissue scar, mostly collagen type I, with increased profibrogenic and proinflammatory molecules gene expression. Matrix metalloproteinase 8 (MMP-8) is an interstitial collagen-degrading proenzyme acting preferentially on collagen type I when activated. This study was carried out to elucidate the effect of an intramuscularly delivered adenoviral vector containing proMMP-8 gene cDNA (AdhMMP8) in male Wistar rats with experimental advanced liver fibrosis induced by thioacetamide. Therapeutic effects were monitored after 1, 2, or 3 weeks of a single dose (3 × 10(11) vp/kg) of AdhMMP8. Circulating and liver concentration of MMP-8 protein remained constant; hepatic fibrosis decreased up to 48%; proinflammatory and profibrogenic genes expression diminished: TNF-α 2.28-fold, IL-1 1.95-fold, Col 1A1 4-fold, TGF-β1 3-fold and CTGF 2-fold; and antifibrogenic genes expression raised, MMP-9 2.8-fold and MMP-1 10-fold. Our data proposes that the administration of AdhMMP8 in muscle is safe and effective in achieving liver fibrosis regression at a comparable extent as when the adenoviral vector is delivered systemically to reach the liver, using a minimally invasive procedure. MDPI 2023-08-22 /pmc/articles/PMC10486800/ /pubmed/37681859 http://dx.doi.org/10.3390/cells12172127 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article García-Bañuelos, Jesús Oceguera-Contreras, Edén Sandoval-Rodríguez, Ana Bastidas-Ramírez, Blanca Estela Lucano-Landeros, Silvia Gordillo-Bastidas, Daniela Gómez-Meda, Belinda C. Santos, Arturo Cerda-Reyes, Eira Armendariz-Borunda, Juan AdhMMP8 Vector Administration in Muscle: An Alternate Strategy to Regress Hepatic Fibrosis |
title | AdhMMP8 Vector Administration in Muscle: An Alternate Strategy to Regress Hepatic Fibrosis |
title_full | AdhMMP8 Vector Administration in Muscle: An Alternate Strategy to Regress Hepatic Fibrosis |
title_fullStr | AdhMMP8 Vector Administration in Muscle: An Alternate Strategy to Regress Hepatic Fibrosis |
title_full_unstemmed | AdhMMP8 Vector Administration in Muscle: An Alternate Strategy to Regress Hepatic Fibrosis |
title_short | AdhMMP8 Vector Administration in Muscle: An Alternate Strategy to Regress Hepatic Fibrosis |
title_sort | adhmmp8 vector administration in muscle: an alternate strategy to regress hepatic fibrosis |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10486800/ https://www.ncbi.nlm.nih.gov/pubmed/37681859 http://dx.doi.org/10.3390/cells12172127 |
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