Research ArticleImmunology

Nuclear PTEN enhances the maturation of a microRNA regulon to limit MyD88-dependent susceptibility to sepsis

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Science Signaling  01 May 2018:
Vol. 11, Issue 528, eaai9085
DOI: 10.1126/scisignal.aai9085

PTEN and sepsis

The uncontrolled production of proinflammatory factors is a leading cause of organ dysfunction during sepsis. As well as being activated by microbial products, Toll-like receptors (TLRs) are activated by injury-associated danger signals. Almost all TLR-dependent cytokine production depends on the adaptor protein MyD88. Sisti et al. found that the abundance of the mRNA encoding the lipid and protein phosphatase PTEN was increased in mice after surgical induction of sepsis. Inhibition or knockdown of PTEN during sepsis resulted in increased inflammation, tissue injury, and mortality, which was associated with an increase in MyD88 abundance. PTEN activation induced the production of microRNAs that targeted Myd88 mRNA. Preventing the nuclear translocation of PTEN resulted in the cytosolic localization of a microRNA-processing complex and a failure to target MyD88. Together, these results suggest that the PTEN-dependent microRNA generation targets MyD88 to limit the damaging effects of sepsis.

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