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Title: Searching for novel molecular targets of chronic rejection in an orthotopic experimental lung transplantation model
Authors: Santana Rodríguez, Norberto 
García-Herrera, Ricardo
Clavo, Bernardino 
Llontop, Pedro
Ponce-González, Miguel A.
Villar, Jesús
López-García, Ana
Fiuza Pérez, Mª Dolores 
Rodríguez-Bermejo, Juan C.
García-Castellano, José M.
MacHín, Rubén P.
Ruíz-Caballero, José A.
Brito, Yanira
Fernández-Pérez, Leandro 
UNESCO Clasification: 32 Ciencias médicas
321314 Cirugía de los trasplantes
Keywords: Bronchiolitis Obliterans Syndrome
Issue Date: 2012
Journal: Journal of Heart and Lung Transplantation 
Abstract: BACKGROUND: Chronic rejection (CR) is the main reason for the limited survival rates among lung transplant (LT) recipients. There remains no effective treatment for CR. The aim of this study was to identify new molecular mechanisms involved in CR by using DNA microarray analysis.METHODS: We performed 10 left LTs using the microsurgical cuff technique in inbred Sprague-Dawley rats. Lung isograft samples were obtained 3 months after surgery. We analyzed histologic, apoptotic and gene expression changes by DNA microarray and quantitative PCR analysis.RESULTS: Histologic analyses confirmed signs of CR in all lungs and positive labeling for apoptotic and anti-apoptotic markers. A total of 702 genes were regulated in the CR lungs: 317 genes were upregulated and 385 were downregulated. Significant changes for about 30 biologic processes, including regulation of the cytoskeleton, and 15 signaling pathways, such as adherens junctions, were observed. We found significantly increased mRNA expression of the Cldn5, Epas1, Tgfb1, Vegf, Selp1, Hsp27 and Igf1 genes.CONCLUSIONS: This is the first experimental study performed in an orthotopic model of LT using DNA microarray analysis. The individual genes, biologic process and pathways identified may represent novel targets that could be manipulated and contribute to the development of treatments capable of providing protection from CR.
ISSN: 1053-2498
DOI: 10.1016/j.healun.2011.11.011
Source: Journal of Heart and Lung Transplantation[ISSN 1053-2498],v. 31, p. 213-221
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