Sorry, you need to enable JavaScript to visit this website.

Transcription Factor ZNF281: A Novel Player in Intestinal Inflammation and Fibrosis

TitleTranscription Factor ZNF281: A Novel Player in Intestinal Inflammation and Fibrosis
Publication TypeArticolo su Rivista peer-reviewed
Year of Publication2018
AuthorsPierdomenico, Maria, Palone Francesca, Cesi Vincenzo, Vitali Roberta, Mancuso A.B., Cucchiara S., Oliva S., Aloi M., and Stronati L.
JournalFrontiers in immunology
Volume9
Pagination2907
ISSN16643224
Keywordsadolescent, animal, Animals, C57BL mouse, Child, colitis, Crohn disease, Dextran Sulfate, enterocolitis, fibrosis, gene expression regulation, genetics, HT-29 cell line, HT29 Cells, human, Humans, Inbred C57BL, Intestinal Mucosa, intestine mucosa, male, metabolism, Mice, Pathology, Trans-Activators, transactivator protein, Ulcerative, ulcerative colitis, ZNF281 protein
Abstract

Background and aims: Recent evidences reveal the occurrence of a close relationship among epithelial to mesenchymal transition (EMT), chronic inflammation and fibrosis. ZNF281 is an EMT-inducing transcription factor (EMT-TF) involved in the regulation of pluripotency, stemness, and cancer. The aim of this study was to investigate in vitro, in vivo, and ex vivo a possible role of ZNF281 in the onset and progression of intestinal inflammation. A conceivable contribution of the protein to the development of intestinal fibrosis was also explored. Methods: Human colorectal adenocarcinoma cell line, HT29, and C57BL/6 mice were used for in vitro and in vivo studies. Mucosal biopsy specimens were taken during endoscopy from 29 pediatric patients with Crohn's disease (CD), 24 with ulcerative colitis (UC) and 16 controls. ZNF281 was knocked down by transfecting HT29 cells with 20 nM small interference RNA (siRNA) targeting ZNF281 (siZNF281). Results: We show for the first time that ZNF281 is induced upon treatment with inflammatory agents in HT29 cells, in cultured uninflamed colonic samples from CD patients and in DSS-treated mice. ZNF281 expression correlates with the disease severity degree of CD and UC patients. Silencing of ZNF281 strongly reduces both inflammatory (IL-8, IL-1beta, IL-17, IL-23) and EMT/fibrotic (SNAIL, Slug, TIMP-1, vimentin, fibronectin, and α-SMA) gene expression; besides, it abolishes the increase of extracellular-collagen level as well as the morphological modifications induced by inflammation. Conclusions: The identification of transcription factor ZNF281 as a novel player of intestinal inflammation and fibrosis allows a deeper comprehension of the pathogenetic mechanisms underlying inflammatory bowel disease (IBD) and provide a new target for their cure.

Notes

cited By 0

URLhttps://www.scopus.com/inward/record.uri?eid=2-s2.0-85059929454&doi=10.3389%2ffimmu.2018.02907&partnerID=40&md5=8d81ff442eed66d8cdc3d749fb32c31d
DOI10.3389/fimmu.2018.02907
Citation KeyPierdomenico20182907