Beneficial effect of STAT3 decoy oligodeoxynucleotide transfection on organ injury and mortality in mice with cecal ligation and puncture-induced sepsis

Autor:	Samar Imbaby, Hiroki Yokoo, Yuichi Hattori, Kohshi Hattori, Naoyuki Matsuda, Sailesh Palikhe, Kengo Tomita
Jazyk:	angličtina
Rok vydání:	2020
Předmět:	Male STAT3 Transcription Factor Chemokine medicine.medical_treatment Genetic enhancement lcsh:Medicine Drug development Punctures HMGB1 Transfection Article Sepsis Mice Medicine Animals RNA Messenger HMGB1 Protein STAT3 lcsh:Science Transcription factor Cecum Ligation Inflammation Mice Inbred BALB C Multidisciplinary biology Molecular medicine business.industry lcsh:R Janus Kinase 2 medicine.disease Disease Models Animal Cytokine Gene Expression Regulation Oligodeoxyribonucleotides biology.protein Cancer research Infectious diseases Cytokines lcsh:Q Chemokines business
Zdroj:	Scientific Reports, Vol 10, Iss 1, Pp 1-16 (2020) Scientific Reports
ISSN:	2045-2322
DOI:	10.1038/s41598-020-72136-x
Popis:	Sepsis is a major clinical challenge with unacceptably high mortality. The signal transducers and activators of transcription (STAT) family of transcription factors is known to activate critical mediators of cytokine responses, and, among this family, STAT3 is implicated to be a key transcription factor in both immunity and inflammatory pathways. We investigated whether in vivo introduction of synthetic double-stranded STAT3 decoy oligodeoxynucleotides (ODNs) can provide benefits for reducing organ injury and mortality in mice with cecal ligation and puncture (CLP)-induced polymicrobial sepsis. We found that STAT3 was rapidly activated in major end-organ tissues following CLP, which was accompanied by activation of the upstream kinase JAK2. Transfection of STAT3 decoy ODNs downregulated pro-inflammatory cytokine/chemokine overproduction in CLP mice. Moreover, STAT3 decoy ODN transfection significantly reduced the increases in tissue mRNAs and proteins of high mobility group box 1 (HMGB1) and strongly suppressed the excessive elevation in serum HMGB1 levels in CLP mice. Finally, STAT3 decoy ODN administration minimized the development of sepsis-driven major end-organ injury and led to a significant survival advantage in mice after CLP. Our results suggest a critical role of STAT3 in the sepsis pathophysiology and the potential usefulness of STAT3 decoy ODNs for sepsis gene therapy.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::75cdc82f4b08e3ffe18e30ce49524b51 http://link.springer.com/article/10.1038/s41598-020-72136-x Zobrazit plný text záznamu Plný text ve formátu PDF Plný text ve formátu HTML
Nepřihlášeným uživatelům se plný text nezobrazuje	K zobrazení výsledku je třeba se přihlásit.