Long non‐coding RNA lnc‐DC in dendritic cells regulates trophoblast invasion via p‐STAT3‐mediated TIMP/MMP expression

Abstract

Problem DCs are the primary antigen‐presenting cells that contact trophoblasts at the beginning of pregnancy. Excessive DCs maturity is described in some pregnancy complications, such as preeclampsia and fetal growth restriction, which are characterized by impaired trophoblast invasion. However, the mechanism is unclear. The long noncoding RNA lnc‐DC is expressed exclusively in conventional human DCs and induces DC differentiation and maturation by promoting STAT3 phosphorylation. Our previous investigation proved lnc‐DC and p‐STAT3 are elevated in preeclampsia. This research is to study the mechanism of lnc‐DC and trophoblast invasion. Method of Study we transfected DCs with lnc‐DC shRNA or a lentivirus for lnc‐DC overexpression, and cocultured these treated DCs with trophoblast under different conditions. Transwell assay and wound healing assay were used to detect the trophoblast invasion ability. We also tested the matured DCs and Th1 cells as well as the p‐STAT3. Results we found that lnc‐DC promoted DC maturation and inhibited trophoblast invasion without the involvement of CD4⁺T cells. And the p‐STAT3 agonist could reverse the lnc‐DC function. Conclusions mature DCs may be involved in altering trophoblast invasion through the overexpression of lnc‐DC, which increases p‐STAT3 levels and the TIMP‐1/MMP‐9 and TIMP‐2/MMP‐2 ratios. Thus, lnc‐DC is a promising novel target for regulating trophoblast invasion.