Abstract:
:Diarrhea-predominant irritable bowel syndrome (IBS-D) is one of the most common gastrointestinal disorders in the world, lacking effective therapies. The crucial roles of microRNAs (miRNAs) in IBS-D have attracted increasing attention. The aim of this study is to investigate the effects of miR-495 on the visceral sensitivity of the IBS-D through the PI3K/AKT signaling pathway by targeting PKIB. Microarray data analysis was employed to screen the differentially expressed genes related to IBS-D and regulatory miRNAs. Then, mice were perfused with acetic acid into the rectum to establish the IBS-D model. Next, PKIB expression was measured in IBS-D mice. Additionally, model mice were injected with a series of adenovirus vector to investigate the influence of miR-495 on visceral sensitivity and rectal function in IBS-D mice with the involvement of PKIB and PI3K/AKT signaling pathway. The IBS-D mouse model was successfully established. PKIB was the target gene of miR-495, and highly expressed in mice with IBS-D. Silencing PKIB reduced visceral sensitivity in mice with IBS-D, and overexpression of miR-495 decreased visceral sensitivity in mice with IBS-D by inhibiting PKIB. Moreover, miR-495 upregulation inhibited PI3K/AKT signaling pathway through downregulating PKIB. To sum up, this study reveals that miR-495 upregulation can reduce visceral sensitivity in IBS-D via inhibition of PI3K/AKT signaling pathway by targeting PKIB. It suggests that miR-495 presents a potential target for IBS-D therapy.
journal_name
IUBMB Lifejournal_title
IUBMB lifeauthors
Fei L,Wang Ydoi
10.1002/iub.2270subject
Has Abstractpub_date
2020-07-01 00:00:00pages
1468-1480issue
7eissn
1521-6543issn
1521-6551journal_volume
72pub_type
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