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Informed target discovery for gene and stem cell therapy in acute lung injury
Author(s) -
Zhou Dun Yuan,
Amatullah Hajera,
Shan Yue Xin,
Gali Patricia,
Hu Ping Zhao,
Santos Claudia C
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.1107.18
Subject(s) - ards , occludin , in silico , sepsis , in vivo , microrna , microarray analysis techniques , microarray , biology , messenger rna , in vitro , medicine , gene expression , immunology , gene , tight junction , lung , microbiology and biotechnology , genetics
Acute lung injury (ALI)/sepsis‐induced acute respiratory distress syndrome (ARDS) accounts for 9% ICU deaths. There is an urgent need for specific treatments and mesenchymal stem cells (MSC) have reparative potential in sepsis and ALI. Methods In the murine model of CLP‐induced ARDS, microarray detected changes in global gene expression following sepsis and MSC treatment. LIMMA analysis identified mRNA and miRNA with significant transcriptional changes between sham, CLP‐operated, and CLP+MSC treated mice. Results We confirmed our in silico data in our in vitro model. Adhesion molecules, occludin and claudin‐2, were putative targets of one miRNA of interest. In silico, occludin was reduced after CLP compared with sham, confirmed by western blots (in vivo and in vitro), and there was a 50% mRNA reduction. Similarly, claudin‐2 expression from the in silico data matched the protein and mRNA analyses (in vivo and in vitro). Subsequently, following transfection of the inhibitor of the miRNA of interest, occludin and claudin‐2′s mRNA levels were observed to be significantly up‐regulated. Conclusion mRNA and miRNA microarrays are informative in identifying candidate therapeutic tools for gene regulation in ARDS treatment. MSC administration after CLP in the murine model acts as a strategy that offers great insight in the detection of therapeutically relevant genes to treat ARDS/ALI.