Skip to main content
Advertisement

Main menu

  • Home
  • Articles
    • Current Issue
    • Fast Forward
    • Latest Articles
    • Special Sections
    • Archive
  • Information
    • Instructions to Authors
    • Submit a Manuscript
    • FAQs
    • For Subscribers
    • Terms & Conditions of Use
    • Permissions
  • Editorial Board
  • Alerts
    • Alerts
    • RSS Feeds
  • Virtual Issues
  • Feedback
  • Submit
  • Other Publications
    • Drug Metabolism and Disposition
    • Journal of Pharmacology and Experimental Therapeutics
    • Molecular Pharmacology
    • Pharmacological Reviews
    • Pharmacology Research & Perspectives
    • ASPET

User menu

  • My alerts
  • Log in
  • My Cart

Search

  • Advanced search
Drug Metabolism & Disposition
  • Other Publications
    • Drug Metabolism and Disposition
    • Journal of Pharmacology and Experimental Therapeutics
    • Molecular Pharmacology
    • Pharmacological Reviews
    • Pharmacology Research & Perspectives
    • ASPET
  • My alerts
  • Log in
  • My Cart
Drug Metabolism & Disposition

Advanced Search

  • Home
  • Articles
    • Current Issue
    • Fast Forward
    • Latest Articles
    • Special Sections
    • Archive
  • Information
    • Instructions to Authors
    • Submit a Manuscript
    • FAQs
    • For Subscribers
    • Terms & Conditions of Use
    • Permissions
  • Editorial Board
  • Alerts
    • Alerts
    • RSS Feeds
  • Virtual Issues
  • Feedback
  • Submit
  • Visit dmd on Facebook
  • Follow dmd on Twitter
  • Follow ASPET on LinkedIn
Research ArticleArticle

MicroRNAs in Apple-Derived Nanoparticles Modulate Intestinal Expression of Organic Anion–Transporting Peptide 2B1/SLCO2B1 in Caco-2 Cells

Hisakazu Komori, Daichi Fujita, Yuma Shirasaki, Qiunan Zhu, Yui Iwamoto, Takeo Nakanishi, Miki Nakajima and Ikumi Tamai
Drug Metabolism and Disposition September 2021, 49 (9) 803-809; DOI: https://doi.org/10.1124/dmd.121.000380
Hisakazu Komori
Department of Membrane Transport and Biopharmaceutics (H.K., D.F., Y.S., Q.Z., Y.I., T.N., I.T.), Department of Drug Metabolism and Toxicology (M.N.), Faculty of Pharmaceutical Sciences, Institute of Medical, Pharmaceutical and Health Sciences, and WPI Nano Life Science Institute (M.N.), Kanazawa University, Kakuma-machi, Kanazawa, Japan
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Daichi Fujita
Department of Membrane Transport and Biopharmaceutics (H.K., D.F., Y.S., Q.Z., Y.I., T.N., I.T.), Department of Drug Metabolism and Toxicology (M.N.), Faculty of Pharmaceutical Sciences, Institute of Medical, Pharmaceutical and Health Sciences, and WPI Nano Life Science Institute (M.N.), Kanazawa University, Kakuma-machi, Kanazawa, Japan
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Yuma Shirasaki
Department of Membrane Transport and Biopharmaceutics (H.K., D.F., Y.S., Q.Z., Y.I., T.N., I.T.), Department of Drug Metabolism and Toxicology (M.N.), Faculty of Pharmaceutical Sciences, Institute of Medical, Pharmaceutical and Health Sciences, and WPI Nano Life Science Institute (M.N.), Kanazawa University, Kakuma-machi, Kanazawa, Japan
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Qiunan Zhu
Department of Membrane Transport and Biopharmaceutics (H.K., D.F., Y.S., Q.Z., Y.I., T.N., I.T.), Department of Drug Metabolism and Toxicology (M.N.), Faculty of Pharmaceutical Sciences, Institute of Medical, Pharmaceutical and Health Sciences, and WPI Nano Life Science Institute (M.N.), Kanazawa University, Kakuma-machi, Kanazawa, Japan
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Yui Iwamoto
Department of Membrane Transport and Biopharmaceutics (H.K., D.F., Y.S., Q.Z., Y.I., T.N., I.T.), Department of Drug Metabolism and Toxicology (M.N.), Faculty of Pharmaceutical Sciences, Institute of Medical, Pharmaceutical and Health Sciences, and WPI Nano Life Science Institute (M.N.), Kanazawa University, Kakuma-machi, Kanazawa, Japan
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Takeo Nakanishi
Department of Membrane Transport and Biopharmaceutics (H.K., D.F., Y.S., Q.Z., Y.I., T.N., I.T.), Department of Drug Metabolism and Toxicology (M.N.), Faculty of Pharmaceutical Sciences, Institute of Medical, Pharmaceutical and Health Sciences, and WPI Nano Life Science Institute (M.N.), Kanazawa University, Kakuma-machi, Kanazawa, Japan
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Miki Nakajima
Department of Membrane Transport and Biopharmaceutics (H.K., D.F., Y.S., Q.Z., Y.I., T.N., I.T.), Department of Drug Metabolism and Toxicology (M.N.), Faculty of Pharmaceutical Sciences, Institute of Medical, Pharmaceutical and Health Sciences, and WPI Nano Life Science Institute (M.N.), Kanazawa University, Kakuma-machi, Kanazawa, Japan
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Ikumi Tamai
Department of Membrane Transport and Biopharmaceutics (H.K., D.F., Y.S., Q.Z., Y.I., T.N., I.T.), Department of Drug Metabolism and Toxicology (M.N.), Faculty of Pharmaceutical Sciences, Institute of Medical, Pharmaceutical and Health Sciences, and WPI Nano Life Science Institute (M.N.), Kanazawa University, Kakuma-machi, Kanazawa, Japan
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • Article
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF + SI
  • PDF
Loading

Visual Overview

Figure
  • Download figure
  • Open in new tab
  • Download powerpoint

Abstract

Plant-derived nanoparticles exert cytoprotective effects on intestinal cells by delivering their cargo to intestinal tissues. We previously reported that apple-derived nanoparticles (APNPs) downregulate the mRNA of the human intestinal transporter organic anion–transporting peptide 2B1 (OATP2B1)/SLCO2B1 and that the 3′-untranslated region (3′UTR) is required for the response to APNPs. Here, we investigated the involvement of microRNAs (miRNAs) in APNPs in suppressing OATP2B1 expression to demonstrate that APNP macromolecules directly interact with intestinal tissues. Using in silico analysis, seven apple miRNAs were predicted as candidate miRNAs that interact with the SLCO2B1-3′UTR. The APNP-mediated decrease in luciferase activity of pGL3/SLCO2B1-3′UTR was abrogated by inhibitors of mdm-miR-160a-e, -7121a-c, or -7121d-h. Each miRNA mimic reduced the endogenous expression of SLCO2B1 mRNA in Caco-2 cells. The luciferase activity of the truncated pGL3/SLCO2B1-3′UTR, which contains approximately 200 bp around each miRNA recognition element (MRE), was decreased by the miR-7121d-h mimic but decreased little by the other mimics. APNP also reduced the luciferase activity of truncated pGL3/SLCO2B1-3′UTR containing an MRE for miR-7121d-h. Thus, we demonstrated that mdm-miR-7121d-h contributes to the APNP-mediated downregulation of intestinal OATP2B1. Accordingly, plant macromolecules, such as miRNAs, may directly interact with intestinal tissues via nanoparticles.

SIGNIFICANCE STATEMENT This study demonstrates that mdm-miR7121d-h contained in apple-derived nanoparticles downregulated the mRNA expression of SLCO2B1 by interacting with SLCO2B1–3′-untranslated region directly and that SLCO2B1 mRNA might also be decreased by mdm-miR160a-e and -7121a-c indirectly. This finding that the specific apple-derived microRNAs influence human intestinal transporters provides a novel concept that macromolecules in foods directly interact with and affect the intestinal function of the host.

Footnotes

    • Received January 19, 2021.
    • Accepted June 1, 2021.
  • This work was supported by Grant-in-Aid for Scientific Research (B) [Grant 16H05111] and Grant-in-Aid for Challenging Exploratory Research [Grant 20K21474] from the Japan Society for the Promotion of Science (JSPS).

  • The authors declare no conflicts of financial interest.

  • https://dx.doi.org/10.1124/dmd.121.000380.

  • ↵Embedded ImageThis article has supplemental material available at dmd.aspetjournals.org.

  • Copyright © 2021 by The American Society for Pharmacology and Experimental Therapeutics
View Full Text

 

DMD articles become freely available 12 months after publication, and remain freely available for 5 years. 

Non-open access articles that fall outside this five year window are available only to institutional subscribers and current ASPET members, or through the article purchase feature at the bottom of the page. 

 

  • Click here for information on institutional subscriptions.
  • Click here for information on individual ASPET membership.

 

Log in using your username and password

Forgot your user name or password?

Purchase access

You may purchase access to this article. This will require you to create an account if you don't already have one.
PreviousNext
Back to top

In this issue

Drug Metabolism and Disposition: 49 (9)
Drug Metabolism and Disposition
Vol. 49, Issue 9
1 Sep 2021
  • Table of Contents
  • Table of Contents (PDF)
  • About the Cover
  • Index by author
  • Editorial Board (PDF)
  • Front Matter (PDF)
Download PDF
Article Alerts
Sign In to Email Alerts with your Email Address
Email Article

Thank you for sharing this Drug Metabolism & Disposition article.

NOTE: We request your email address only to inform the recipient that it was you who recommended this article, and that it is not junk mail. We do not retain these email addresses.

Enter multiple addresses on separate lines or separate them with commas.
MicroRNAs in Apple-Derived Nanoparticles Modulate Intestinal Expression of Organic Anion–Transporting Peptide 2B1/SLCO2B1 in Caco-2 Cells
(Your Name) has forwarded a page to you from Drug Metabolism & Disposition
(Your Name) thought you would be interested in this article in Drug Metabolism & Disposition.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Citation Tools
Research ArticleArticle

Regulation of OATP2B1 by Apple miRNA in Nanoparticles

Hisakazu Komori, Daichi Fujita, Yuma Shirasaki, Qiunan Zhu, Yui Iwamoto, Takeo Nakanishi, Miki Nakajima and Ikumi Tamai
Drug Metabolism and Disposition September 1, 2021, 49 (9) 803-809; DOI: https://doi.org/10.1124/dmd.121.000380

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero

Share
Research ArticleArticle

Regulation of OATP2B1 by Apple miRNA in Nanoparticles

Hisakazu Komori, Daichi Fujita, Yuma Shirasaki, Qiunan Zhu, Yui Iwamoto, Takeo Nakanishi, Miki Nakajima and Ikumi Tamai
Drug Metabolism and Disposition September 1, 2021, 49 (9) 803-809; DOI: https://doi.org/10.1124/dmd.121.000380
del.icio.us logo Digg logo Reddit logo Twitter logo Facebook logo Google logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Jump to section

  • Article
    • Visual Overview
    • Abstract
    • Introduction
    • Materials and Methods
    • Results
    • Discussion
    • Authorship Contributions
    • Footnotes
    • Abbreviations
    • References
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF + SI
  • PDF

Related Articles

Cited By...

More in this TOC Section

  • Oral PBPK Modeling of Vismodegib
  • Transporter-enzyme interplay in PK of PF-06835919
  • PBPK Model of Vit D3 and Metabolites
Show more Articles

Similar Articles

Advertisement
  • Home
  • Alerts
Facebook   Twitter   LinkedIn   RSS

Navigate

  • Current Issue
  • Fast Forward by date
  • Fast Forward by section
  • Latest Articles
  • Archive
  • Search for Articles
  • Feedback
  • ASPET

More Information

  • About DMD
  • Editorial Board
  • Instructions to Authors
  • Submit a Manuscript
  • Customized Alerts
  • RSS Feeds
  • Subscriptions
  • Permissions
  • Terms & Conditions of Use

ASPET's Other Journals

  • Journal of Pharmacology and Experimental Therapeutics
  • Molecular Pharmacology
  • Pharmacological Reviews
  • Pharmacology Research & Perspectives
ISSN 1521-009X (Online)

Copyright © 2022 by the American Society for Pharmacology and Experimental Therapeutics