title: MicroRNA-29a mediates the impairment of intestinal epithelial integrity induced by intrauterine growth restriction in pig.
abstract: An important characteristic of intrauterine growth restricted (IUGR) neonate is the impaired intestinal barrier function. With the use of a pig model, this study was conducted to identify the responsible microRNA (miRNA) for the intestinal damage in IUGR neonates through comparing the miRNA profile of IUGR and normal porcine neonates and to investigate the regulation mechanism. Compared with the normal ones, we identified 83 upregulated and 76 downregulated miRNAs in the jejunum of IUGR pigs. Notably, IUGR is associated with profoundly increasesd miR-29 family and decreased expression of extracellular matrix (ECM) and tight junction (TJ) proteins in the jejunum. Furthermore, in vitro study using theporcine intestinal epithelial cell line (IPEC-1) showed that inhibition of miR-29a expression could improve the monolayer integrity by increasing cell proliferation and transepithelial resistance. Also, overexpression/inhibition of miR-29a in IPEC-1 cells can suppress/increase the expression of integrin-β1, collagen I, collagen IV, fibronectin, and claudin 1, both at transcriptional and translational levels. Subsequent luciferase reporter assay confirmed a direct interaction between miR-29a and the 3'-untranslated regions of these genes. In conclusion, this study reveals that IUGR-impaired intestinal barrier function is associated with downregulated ECM and TJ protein expression mediated by the upregulation of miR-29a.NEW & NOTEWORTHYIntrauterine growth restricted (IUGR) remains a major problem for both human health and animal production due to its association with high rates of preweaning morbidity and mortality. We have identified the abnormal expression of microRNA-29a (miR-29a) in the small intestine of IUGR neonates, as well as its targets and mechanisms. These results provide new information about biological characteristics of IUGR-affected intestinal dysfunction and can lead to the development of potentially solution for preventing and treating IUGR in the future.
authors.affiliation: State Key Laboratory of Animal Nutrition, College of Animal Science and Technology, China, Agricultural University, Beijing, China.
authors.forename: Yuhua
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: State Key Laboratory of Animal Nutrition, College of Animal Science and Technology, China, Agricultural University, Beijing, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Animal Nutrition, College of Animal Science and Technology, China, Agricultural University, Beijing, China.
authors.forename: Taolin
authors.initials: T
authors.lastname: Yuan
authors.affiliation: Key Laboratory of Agricultural Animal Genetics, Breeding and Reproduction, Huazhong Agricultural University, Wuhan, Hubei, China.
authors.forename: Liangliang
authors.initials: L
authors.lastname: Fu
authors.affiliation: Key Laboratory of Agricultural Animal Genetics, Breeding and Reproduction, Huazhong Agricultural University, Wuhan, Hubei, China.
authors.forename: Lian
authors.initials: L
authors.lastname: Zhou
authors.affiliation: State Key Laboratory of Animal Nutrition, College of Animal Science and Technology, China, Agricultural University, Beijing, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Lin
authors.affiliation: Key Laboratory of Agricultural Animal Genetics, Breeding and Reproduction, Huazhong Agricultural University, Wuhan, Hubei, China.
authors.forename: Shuhong
authors.initials: S
authors.lastname: Zhao
authors.affiliation: Department of Animal Science, University of California, Davis, California; and.
authors.forename: Huaijun
authors.initials: H
authors.lastname: Zhou
authors.affiliation: State Key Laboratory of Animal Nutrition, College of Animal Science and Technology, China, Agricultural University, Beijing, China.|Department of Animal Science, Texas A&M University, College Station, Texas.
authors.forename: Guoyao
authors.initials: G
authors.lastname: Wu
authors.affiliation: State Key Laboratory of Animal Nutrition, College of Animal Science and Technology, China, Agricultural University, Beijing, China; jkywjj@hotmail.com.
authors.forename: Junjun
authors.identifier: http://orcid.org/0000-0001-9427-3824
authors.initials: J
authors.lastname: Wang
mesh_terms: D000818:Animals; D005317:Fetal Growth Retardation / Q000378:metabolism* / Q000473:pathology; D007408:Intestinal Absorption; D007413:Intestinal Mucosa / Q000196:embryology / Q000378:metabolism* / Q000473:pathology; D007583:Jejunum / Q000196:embryology / Q000378:metabolism* / Q000473:pathology; D035683:MicroRNAs / Q000378:metabolism; D013552:Swine
chemical_list: D035683:MicroRNAs
keywords: IUGR; extracellular matrix; intestinal permeability; miRNA microarray; tight junction