Colon Epithelial MicroRNA Network in Fatty Liver.

Authors:
Dr. Paule V Joseph, PhD, RN, MS, FNP-BC, CTN-B
Dr. Paule V Joseph, PhD, RN, MS, FNP-BC, CTN-B
National Institute of Nursing Research
Tenure-Track Investigator (Clinical)
N/A
Bethesda , Maryland | United States
Sarah K Abey
Sarah K Abey
National Institutes of Health
United States
Dan Wang
Dan Wang
College of Life Sciences
Provo | United States
Nicolaas H Fourie
Nicolaas H Fourie
University of Cape Town
South Africa
Natnael D Kenea
Natnael D Kenea
National Institutes of Health
Tatyana G Vishnyakova
Tatyana G Vishnyakova
National Institutes of Health
United States
Jeffrey M Robinson
Jeffrey M Robinson
Dartmouth College
Hanover | United States
Kristen R Weaver
Kristen R Weaver
National Institutes of Health
Bethesda | United States

Can J Gastroenterol Hepatol 2018 24;2018:8246103. Epub 2018 Sep 24.

Digestive Disorder Unit, Division of Intramural Research, National Institute of Nursing Research, National Institutes of Health, Bethesda, MD 20892, USA.

Background & Aims: Intestinal barrier alterations are associated with fatty liver (FL) and metabolic syndrome (MetS), but microRNA (miR) signaling pathways in MetS-FL pathogenesis remain unclear. This study investigates an epithelial-focused miR network in colorectal cell models based on the previously reported MetS-FL miR trio of hsa-miR-142-3p, hsa-miR-18b, and hsa-miR-890.

Methods: Each miR mimic construct of MetS-FL miR trio was transfected into human colorectal cells, CRL-1790 or Caco-2. Global miRNome changes posttransfection were profiled (nCounter® Human v3 miRNA, NanoString Technologies). Changes in barrier (transepithelial electrical resistance, TEER) and epithelial cell junction structure (Occludin and Zona Occludens-1/ZO-1 immunofluorescence staining-confocal microscopy) were examined pre- and posttransfection in Caco-2 cell monolayers. A signaling network was constructed from the MetS-FL miR trio, MetS-FL miR-induced colorectal miRNome changes, ZO-1, and Occludin.

Results: Transfection of CRL-1790 cells with each MetS-FL miR mimic led to global changes in the cellular miRNome profile, with 288 miRs being altered in expression by more than twofold. Eleven miRs with known cytoskeletal and metabolic roles were commonly altered in expression by all three miR mimics. Transfection of Caco-2 cell monolayers with each MetS-FL miR mimic induced barrier-associated TEER variations and led to structural modifications of ZO-1 and Occludin within epithelial cell junctions. Pathway analysis incorporating the MetS-FL miR trio, eleven common target miRs, ZO-1, and Occludin revealed a signaling network centered on TNF and AKT2, which highlights injury, inflammation, and hyperplasia.

Conclusions: Colon-specific changes in epithelial barriers, cell junction structure, and a miRNome signaling network are described from functional studies of a MetS-FL miR trio signature.

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Source
https://www.hindawi.com/journals/cjgh/2018/8246103/
Publisher Site
http://dx.doi.org/10.1155/2018/8246103DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6174781PMC
March 2019
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