Role of differentially expressed microRNA-139-5p in the regulation of phenotypic internal anal sphincter smooth muscle tone.

Authors

Jagmohan Singh, Thomas Jefferson UniversityFollow
Ipsita Mohanty, Thomas Jefferson UniversityFollow
Sankar Addya, Thomas Jefferson UniversityFollow
Benjamin Philllips, Thomas Jefferson UniversityFollow
Hwan Mee Yong, Johns Hopkins Bloomberg School of Public Health
Steven S. An, Johns Hopkins Bloomberg School of Public HealthFollow
Raymond B. Penn, Thomas Jefferson UniversityFollow
Satish Rattan, Thomas Jefferson UniversityFollow

Document Type

Article

Publication Date

5-3-2017

Comments

This article has been peer reviewed. It is the author’s final published version in Scientific Reports

Volume 7, Issue 1, May 2017, Article number 1477

The published version is available at DOI: 10.1038/s41598-017-01550-5. Copyright © Singh et al.

Abstract

The present study focused on the role of microRNA-139-5p (miRNA-139-5p) in the regulation of basal tone in internal anal sphincter (IAS). Applying genome-wide miRNA microarrays on the phenotypically distinct smooth muscle cells (SMCs) within the rat anorectrum, we identified miRNA-139-5p as differentially expressed RNA repressor with highest expression in the purely phasic smooth muscle of anococcygeus (ASM) vs. the truly tonic smooth muscle of IAS. This pattern of miRNA-139-5p expression, previously shown to target ROCK2, was validated by target prediction using ingenuity pathway (IPA) and by qPCR analyses. Immunoblotting, immunocytochemistry (ICC), and functional assays using IAS tissues and cells subjected to overexpression/knockdown of miRNA-139-5p confirmed the inverse relationship between miRNA-139-5p and ROCK2 expressions/IAS tone. Overexpression of miRNA-139-5p caused a decrease, while knockdown by anti-miRNA-139-5p caused an increase in the IAS tone; these tissue contractile responses were confirmed by single-cell contraction using magnetic twisting cytometry (MTC). These findings suggest miRNA-139-5p is capable of significantly influencing the phenotypic tonicity in smooth muscle via ROCK2: a lack of tone in ASM may be associated with the suppression of ROCK2 by high expression of miRNA-139-5p, whereas basal IAS tone may be associated with the persistence of ROCK2 due to low expression of miRNA-139-5p.

Recommended Citation

Singh, Jagmohan; Mohanty, Ipsita; Addya, Sankar; Philllips, Benjamin; Mee Yong, Hwan; An, Steven S.; Penn, Raymond B.; and Rattan, Satish, "Role of differentially expressed microRNA-139-5p in the regulation of phenotypic internal anal sphincter smooth muscle tone." (2017). Division of Gastroenterology and Hepatology Faculty Papers. Paper 40.
https://jdc.jefferson.edu/gastro_hepfp/40

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 License.

PubMed ID

28469189