RNA regulons are essential in intestinal homeostasis
AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY
Authors: Parham, Louis R.; Williams, Patrick A.; Chatterji, Priya; Whelan, Kelly A.; Hamilton, Kathryn E.
Abstract
Intestinal epithelial cells are among the most rapidly proliferating cell types in the human body. There are several different subtypes of epithelial cells, each with unique functional roles in responding to the ever-changing environment. The epithelium's ability for rapid and customized responses to environmental changes requires multitiered levels of gene regulation. An emerging paradigm in gastrointestinal epithelial cells is the regulation of functionally related mRNA families, or regulons, via RNA-binding proteins (RBPs). RBPs represent a rapid and efficient mechanism to regulate gene expression and cell function. In this review, we will provide an overview of intestinal epithelial RBPs and how they contribute specifically to intestinal epithelial stem cell dynamics. In addition, we will highlight key gaps in knowledge in the global understanding of RBPs in gastrointestinal physiology as an opportunity for future studies.
Downregulated low-density lipoprotein receptor-related protein 6 induces the maldevelopment of extravillous trophoblast via Wnt/beta-catenin signaling pathway
MOLECULAR AND CELLULAR PROBES
Authors: Yu, Xiaoyan; Zhang, Yan; Yang, Ping; Gao, Xueli; Wang, Yuping
Abstract
Preeclampsia (PE), a special type of hypertensive disorder complicating pregnancy (HDCP), is highly associated with the migratory and invasive capacity of extravillous trophoblasts (EVTs). Here, we aimed to study the functions of low-density lipoprotein receptor-related protein 6 (LRP6) in PE pathogenesis. A comparative analysis of cellular gene expressions between placenta tissues collected from PE patients and normal pregnant women showed that the expressions of LRP6, beta-catenin and matrix metallopeptidases/TIMP metallopeptidase inhibitors (MMPs/TIMPs) ratio in placentas of PE patients were much lower than the normal. Then, we constructed and transfected LRP6 siRNA (siLRP6) and LRP6 overexpression vectors into HTR6/SVneo cells. On the contrary to siLRP6, LRP6 overexpression could significant enhance cell viability, and strengthen the abilities of cell migration and invasion. Importantly, the overexpression of LRP6 could induce the upregulation of MMP-2 and MMP-9 levels, and downregulation of TIMPs. The mRNA and protein levels of beta-catenin, an intracellular signal transducer of Wnt signaling pathway, were significantly up-regulated under the effects of LRP6 overexpression. XAV939, a Wnt/beta-catenin pathway inhibitor, was introduced to confirm the involvement of Wnt/beta-catenin pathway in functions of LRP6. The results of cell viability detection showed that XAV939 could significantly inhibit the positive effects of LRP6 overexpression on cell viability. Taken together, low-expressed LRP6 may be responsible of lower migration and invasion of EVTs and subsequent PE, and the mechanisms show a highly association with Wnt/beta-catenin pathway.