AdhMMP8 Vector Administration in Muscle: An Alternate Strategy to Regress Hepatic Fibrosis
Jesús García-Bañuelos,
Edén Oceguera-Contreras,
Ana Sandoval-Rodríguez,
Blanca Estela Bastidas-Ramírez,
Silvia Lucano-Landeros,
Daniela Gordillo-Bastidas,
Belinda C. Gómez-Meda,
Arturo Santos,
Eira Cerda-Reyes,
Juan Armendariz-Borunda
Affiliations
Jesús García-Bañuelos
Institute for Molecular Biology in Medicine and Gene Therapy, Department of Molecular Biology and Genomics, Health Sciences University Center, University of Guadalajara, Guadalajara 44340, Jalisco, Mexico
Edén Oceguera-Contreras
Laboratorio de Sistemas Biológicos, Centro Universitario de los Valles, Universidad de Guadalajara, Carretera Guadalajara-Ameca km. 45.5, Ameca 46600, Jalisco, Mexico
Ana Sandoval-Rodríguez
Institute for Molecular Biology in Medicine and Gene Therapy, Department of Molecular Biology and Genomics, Health Sciences University Center, University of Guadalajara, Guadalajara 44340, Jalisco, Mexico
Blanca Estela Bastidas-Ramírez
Instituto de Investigación en Enfermedades Crónico Degenerativas, Department of Molecular Biology and Genomics, Health Sciences University Center, University of Guadalajara, Guadalajara 44340, Jalisco, Mexico
Silvia Lucano-Landeros
Institute for Molecular Biology in Medicine and Gene Therapy, Department of Molecular Biology and Genomics, Health Sciences University Center, University of Guadalajara, Guadalajara 44340, Jalisco, Mexico
Daniela Gordillo-Bastidas
Tecnologico de Monterrey, Escuela de Medicina y Ciencias de la Salud, Monterrey 64849, Nuevo Leon, Mexico
Belinda C. Gómez-Meda
Instituto de Genética Humana “Dr. Enrique Corona Rivera”, Department of Molecular Biology and Genomics, Health Sciences University Center, Guadalajara 44340, Jalisco, Mexico
Arturo Santos
Tecnologico de Monterrey, Escuela de Medicina y Ciencias de la Salud, Monterrey 64849, Nuevo Leon, Mexico
Eira Cerda-Reyes
Hospital Central Militar, Mexico City 11600, Mexico
Juan Armendariz-Borunda
Institute for Molecular Biology in Medicine and Gene Therapy, Department of Molecular Biology and Genomics, Health Sciences University Center, University of Guadalajara, Guadalajara 44340, Jalisco, Mexico
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 × 1011 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.
