Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2020 Sep 1;35(5):328-337.
doi: 10.1152/physiol.00011.2020.

Polyamines in Gut Epithelial Renewal and Barrier Function

Jaladanki N Rao  1   2 , Lan Xiao  1   2 , Jian-Ying Wang  1   2   3
Affiliations
Review

Polyamines in Gut Epithelial Renewal and Barrier Function

Jaladanki N Rao et al. Physiology (Bethesda). .

Abstract

Polyamines regulate a variety of physiological functions and are involved in pathogenesis of diverse human diseases. The epithelium of the mammalian gut mucosa is a rapidly self-renewing tissue in the body, and its homeostasis is preserved through well-controlled mechanisms. Here, we highlight the roles of cellular polyamines in maintaining the integrity of the gut epithelium, focusing on the emerging evidence of polyamines in the regulation of gut epithelial renewal and barrier function. Gut mucosal growth depends on the available supply of polyamines to the dividing cells in the crypts, and polyamines are also essential for normal gut epithelial barrier function. Polyamines modulate expression of various genes encoding growth-associated proteins and intercellular junctions via distinct mechanisms involving RNA-binding proteins and noncoding RNAs. With the rapid advance of polyamine biology, polyamine metabolism and transport are promising therapeutic targets in our efforts to protect the gut epithelium and barrier function in patients with critical illnesses.

Keywords: RNA-binding proteins; gut epithelial homeostasis; noncoding RNAs; polyamine biosynthesis; posttranscriptional regulation.

PubMed Disclaimer

Figures

FIGURE 1.
FIGURE 1.
Polyamine biosynthesis and catabolism ODC, ornithine decarboxylase; SAMDC, S-adenosylmethionine decarboxylase; DFMO, α-difluoromethylornithine. Putrescine, spermidine, and spermine carry two, three, and four positive-charge free amine groups, respectively, which reflects the strength of their binding ability in cells.
FIGURE 2.
FIGURE 2.
Polyamine depletion inhibits gut epithelial renewal by increasing the expression of growth-inhibiting genes via HuR Polyamines are essential for the nuclear accumulation of HuR through activation of AMP-activated protein kinase 1 (AMPK1) and acetylation (Ac) of importin α1. Polyamine depletion increases cytoplasmic HuR levels by repressing AMPK1-dependent HuR phosphorylation (P). Cytoplasmic HuR in polyamine-deficient cells directly interacts with and increases the stability and translation of mRNAs encoding growth-inhibiting proteins, leading to an inhibition of gut epithelial renewal.
FIGURE 3.
FIGURE 3.
Polyamines regulate gut barrier function by altering HuR interaction with lncRNAs SPRY4-IT1 and H19 Polyamines increase SPRY4-IT1 association with TJ mRNAs but prevent miR-675 processing from H19 via regulation of HuR binding affinity, thus enhancing IJ expression and promoting gut epithelial barrier function.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Akaike Y, Masuda K, Kuwano Y, Nishida K, Kajita K, Kurokawa K, Satake Y, Shoda K, Imoto I, Rokutan K. HuR regulates alternative splicing of the TRA2β gene in human colon cancer cells under oxidative stress. Mol Cell Biol 34: 2857–2873, 2014. doi:10.1128/MCB.00333-14. - DOI - PMC - PubMed
    1. Bachmann AS, Geerts D. Polyamine synthesis as a target of MYC oncogenes. J Biol Chem 293: 18757–18769, 2018. doi:10.1074/jbc.TM118.003336. - DOI - PMC - PubMed
    1. Batista PJ, Chang HY. Long noncoding RNAs: cellular address codes in development and disease. Cell 152: 1298–1307, 2013. doi:10.1016/j.cell.2013.02.012. - DOI - PMC - PubMed
    1. Bekebrede AF, Keijer J, Gerrits WJJ, Boer VCJ. The molecular and physiological effects of protein-derived polyamines in the intestine. Nutrients 12: 197, 2020. doi:10.3390/nu12010197. - DOI - PMC - PubMed
    1. Bergalet J, Fawal M, Lopez C, Desjobert C, Lamant L, Delsol G, Morello D, Espinos E. HuR-mediated control of C/EBPbeta mRNA stability and translation in ALK-positive anaplastic large cell lymphomas. Mol Cancer Res 9: 485–496, 2011. doi:10.1158/1541-7786.MCR-10-0351. - DOI - PubMed

Publication types

LinkOut - more resources