A Novel Role for SIRT3 in Regulating Mediators Involved in the Terminal Pathways of Human Labor and Delivery.

In this study, we determined the effect of term labor and pro-inflammatory cytokines on SIRT3, SIRT4, SIRT5 and SIRT7 expression in human myometrium. Functional studies were also employed to investigate the effect of siRNA knockdown of SIRTs in regulating inflammation-induced pro-labor mediators. Western blot analysis and qRT-PCR were used to determine SIRT3, SIRT4, SIRT5 and SIRT7 mRNA and protein expression in human myometrium. siRNA knockdown of SIRT3 in myometrial primary cells determined its role in response to inflammatory stimuli IL1B and TNF. SIRT3 mRNA and protein expression were significantly lower in term laboring myometrium compared with term non-laboring myometrium. There was no effect of labor on SIRT4, SIRT5 or SIRT7 protein expression. The pro-inflammatory cytokines IL1B and TNF significantly decreased SIRT3 mRNA and protein expression. SIRT3 knockdown by siRNA significantly augmented IL1B- and TNF-stimulated IL6, CXCL8 and CCL2 mRNA expression and release; PTGS2 mRNA expression and subsequent PGF2α release; the mRNA expression and secretion of the adhesion molecule ICAM1 and the extracellular matrix remodelling enzyme MMP9; and NFKB1 transcriptional activity. In human myometrium, SIRT3 expression decreases with term labor and regulates the mediators involved in the terminal effector pathways of human labor and delivery via the NFKB1 pathway. PMID: 27628218 [PubMed - as supplied by publisher]
Source: Biology of Reproduction - Category: Reproduction Medicine Authors: Tags: Biol Reprod Source Type: research