Hyaluronic acid promotes Lgr5+ stem cell proliferation and crypt fission through TLR4 and PGE2 transactivation of EGFR.

American Journal of Physiology. Gastrointestinal and Liver Physiology
Terrence E RiehlWilliam F Stenson

Abstract

Hyaluronic acid (HA), a glycosaminoglycan in the extracellular matrix, binds to CD44 and Toll-like receptor 4 (TLR4). We previously demonstrated that both CD44 and TLR4, but predominately TLR4, mediated HA stimulation of Lgr5+ stem cell proliferation, crypt fission, and intestinal growth in postnatal mice. Here we address the questions of which cell type expresses the relevant TLR4 in driving intestinal growth and what are the downstream events from TLR4 activation. Studies were done in 14-day-old mice: wild type (WT), mice deficient in cyclooxygenase 2 (COX2), mice deficient in myeloid cell TLR4, and mice deficient in epithelial cell epidermal growth factor receptor (EGFR). Biological end points included crypt fission and Lgr5 cell proliferation. In WT mice, treatment with NS-398 (a COX2 inhibitor), clodronate (a macrophage-depleting agent), or tyrphostin (an EGFR inhibitor) resulted in 30% reductions in crypt fission and Lgr5+ stem cell proliferation compared with control mice. Mice deficient in COX2 or myeloid TLR4 or epithelial cell EGFR all had 30% reductions in crypt fission and Lgr5+ stem cell proliferation compared with WT mice. Administration of dimethyl PGE2, a stable PGE2 analog, increased crypt fission and Lgr5+ ste...Continue Reading

References

Nov 1, 1983·The Journal of Pharmacy and Pharmacology·U Förstermann, B Neufang
Sep 20, 2000·The Journal of Experimental Medicine·M E MummertA Takashima
Jun 26, 2003·The Journal of Biological Chemistry·F Gregory BuchananRaymond N DuBois
Dec 24, 2004·Proceedings of the National Academy of Sciences of the United States of America·Sarah L PullThaddeus S Stappenbeck
Apr 19, 2005·Genes & Development·Alex Gregorieff, Hans Clevers
Apr 28, 2005·The Journal of Biological Chemistry·Teruhisa NomuraVictor L Schuster
Oct 26, 2005·Nature Medicine·Dianhua JiangPaul W Noble
Jan 4, 2007·The Journal of Clinical Investigation·Sarah L BrownThaddeus S Stappenbeck
Jan 24, 2007·Nature Genetics·Xi C HeLinheng Li
Feb 28, 2008·Current Opinion in Gastroenterology·William F Stenson
Aug 15, 2008·Proceedings of the National Academy of Sciences of the United States of America·Toshimitsu YamaokaD Brent Polk
Jul 11, 2009·American Journal of Physiology. Gastrointestinal and Liver Physiology·Christopher M DekaneySusan J Henning
Dec 19, 2009·The Journal of Biological Chemistry·Monica R WalkerThaddeus S Stappenbeck
Aug 18, 2010·Laboratory Investigation; a Journal of Technical Methods and Pathology·Atsushi SuzukiHideki Taniguchi
Nov 22, 2011·PloS One·Jeffrey J DehmerMichael A Helmrath
Jan 20, 2012·Mucosal Immunology·Nicole P MalvinThaddeus S Stappenbeck
May 5, 2012·American Journal of Physiology. Gastrointestinal and Liver Physiology·Terrence E RiehlWilliam F Stenson
Jun 12, 2012·Cell·Hans Clevers, Roel Nusse
Dec 25, 2013·The Journal of Biological Chemistry·Milena SokolowskaJames H Shelhamer
May 24, 2015·Cellular and Molecular Life Sciences : CMLS·Shiyan Yu, Nan Gao
Jul 15, 2015·Gastroenterology·Kyle C RocheScott T Magness
Oct 28, 2015·American Journal of Physiology. Gastrointestinal and Liver Physiology·Terrence E RiehlWilliam F Stenson
Mar 30, 2018·Nature Communications·Anuj SehgalNeil A Mabbott

❮ Previous
Next ❯

Software Mentioned

GraphPad Prism

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.