Online citations, reference lists, and bibliographies.
← Back to Search

Regulation Of Chitosan-mediated Differentiation Of Human Olfactory Receptor Neurons By Insulin-like Growth Factor Binding Protein-2.

T. Huang, Sheng-Tien Li, Yu-Hsin Wang, T. Young
Published 2019 · Chemistry, Medicine

Save to my Library
Download PDF
Analyze on Scholarcy
Share
Olfaction is normally taken for granted in our lives, not only assisting us to escape from dangers, but also increasing our quality of life. Although olfactory neuroepithelium (ON) can reconstitute its olfactory receptor neurons (ORNs) after injury, no adequate treatment for olfactory loss has yet emerged. The present study investigates the role of glycosaminoglycans (GAGs) in modulating olfactory neuronal homeostasis and elucidates the regulatory mechanism. This work isolates and cultures human olfactory neuroepithelial cells (HONCs) with various GAGs for 7 days, and find that chitosan promotes ORN maturation, expressing olfactory marker protein (OMP) and its functional components. Growth factor protein array, ELISA and western blot analysis reveal that insulin-like growth factor binding protein 2 (IGFBP2) shows a higher level in chitosan-treated HONCs than in controls. Biological activity of insulin-like growth factor-1 (IGF-1), IGF-2 and IGF-1 receptor (IGF1R) is further investigated. Experimental results indicate that IGF-1 and IGF-2 enhance the growth of immature ORNs, expressing βIII tubulin, but decrease mature ORNs. Instead, down-regulation of phosphorylated IGF1R lifts the OMP expression, and lowers the βIII tubulin expression, by incubation with the phosphorylated inhibitor of IGF1R, OSI-906. Finally, the effect of chitosan on ORN maturity is antagonized by concurrently adding IGFBP2 protease, matrix metallopeptidase-1. Overall, our data demonstrate that chitosan promotes ORN differentiation by raising the level of IGFBP2 to sequestrate the IGFs-IGF1R signaling. STATEMENT OF SIGNIFICANCE: Olfactory dysfunction serves as a crucial alarm in neurodegenerative diseases, and one of its causes is lacking of sufficient mature olfactory receptor neurons to detect odorants in the air. However, the clinical treatment for olfactory dysfunction is still controversial. Chitosan is the natural linear polysaccharide and exists in rat olfactory neuroepithelium. Previously, chitosan has been demonstrated to mediate the differentiation of olfactory receptor neurons in an in vitro rat model, but the mechanism is unknown. The study aims to evaluate the role and mechanism of chitosan in an in vitro human olfactory neurons model. Overall, these results reveal that chitosan is a potential agent for treating olfactory disorder by the maintenance of olfactory neural homeostasis. This is the first report to demonstrate that chitosan promotes differentiation of olfactory receptor neurons through increasing IGFBP2 to sequestrate the IGFs-IGF1R.
This paper references
10.1073/pnas.1701333114
Notch1 maintains dormancy of olfactory horizontal basal cells, a reserve neural stem cell
D. Herrick (2017)
10.1242/jeb.035162
Chitosan produces potent neuroprotection and physiological recovery following traumatic spinal cord injury
Youngnam Cho (2010)
10.1016/S0306-4522(99)00193-1
Olfactory receptor neurons exist as distinct subclasses of immature and mature cells in primary culture
A. Cunningham (1999)
10.1097/00005537-200101000-00002
The Diagnosis of a Conductive Olfactory Loss
A. Seiden (2001)
10.1007/s00418-002-0407-1
On the chemosensory nature of the vomeronasal epithelium in adult humans
M. Witt (2002)
10.1177/194589240401800107
Local and Systemic Administration of Corticosteroids in the Treatment of Olfactory Loss
Stefan Heilmann (2004)
10.1038/s41467-018-07544-9
Olfactory marker protein (OMP) regulates formation and refinement of the olfactory glomerular map
D. F. Albeanu (2018)
10.1002/term.2274
Chitosan promotes aquaporin formation and inhibits mucociliary differentiation of nasal epithelial cells through increased TGF‐β1 production
T. Huang (2017)
10.1021/bm800276d
Why is chitosan mucoadhesive?
Ioannis A Sogias (2008)
10.1073/pnas.1613026113
Development of the main olfactory system and main olfactory epithelium-dependent male mating behavior are altered in Go-deficient mice
Jung-Mi Choi (2016)
10.1016/S0006-8993(99)01614-5
Mucus of the human olfactory epithelium contains the insulin-like growth factor-I system which is altered in some neurodegenerative diseases
G. Federico (1999)
10.1111/j.1460-9568.2005.04355.x
Regulation of adult olfactory neurogenesis by insulin‐like growth factor‐I
R. Mccurdy (2005)
10.1002/lary.21856
Immunohistochemical characterization of human olfactory tissue
E. Holbrook (2011)
10.1093/chemse/bju043
The impact of olfactory disorders in the United kingdom.
C. Philpott (2014)
10.1016/J.BIOMATERIALS.2003.11.029
The interaction of Schwann cells with chitosan membranes and fibers in vitro.
Ying Yuan (2004)
10.1021/bm5007954
Structure of chitosan determines its interactions with mucin.
B. Menchicchi (2014)
10.1006/exnr.1998.6810
Primary Culture of Adult Mouse Olfactory Receptor Neurons
N. Liu (1998)
10.1177/194589240501900115
Endoscopic Biopsy of Human Olfactory Epithelium as a Source of Progenitor Cells
W. Winstead (2005)
10.4103/1673-5374.163466
Chitosan-collagen porous scaffold and bone marrow mesenchymal stem cell transplantation for ischemic stroke
F. Yan (2015)
10.1016/j.devcel.2018.07.010
FGF20-Expressing, Wnt-Responsive Olfactory Epithelial Progenitors Regulate Underlying Turbinate Growth to Optimize Surface Area.
Lu M. Yang (2018)
10.4193/Rhin17.155
Chitosan films promote formation of olfactory neurospheres and differentiation of olfactory receptor neurons.
S. T. Li (2018)
10.1016/j.schres.2013.08.013
Proteoglycan abnormalities in olfactory epithelium tissue from subjects diagnosed with schizophrenia
H. Pantazopoulos (2013)
10.1002/2211-5463.12330
Matrix metalloproteinase‐1 facilitates MSC migration via cleavage of IGF‐2/IGFBP2 complex
S. P. Guan (2018)
10.1210/ENDO.138.11.5472
Insulin-like growth factor binding protein-2 binds to cell surface proteoglycans in the rat brain olfactory bulb.
V. Russo (1997)
10.1016/j.actbio.2017.12.029
Poly (ethylene-co-vinyl alcohol) is a suitable substrate for human olfactory neuroepithelial cell differentiation in vitro through a defined regulatory pathway.
Sheng-Tien Li (2018)
10.1038/nrm1050
Mannose 6-phosphate receptors: new twists in the tale
P. Ghosh (2003)
10.1007/BF00327769
Lectin histochemical localization of galactose, N-acetylgalactosamine, and N-acetylglucosamine in glycoconjugates of the rat vomeronasal organ, with comparison to the olfactory and septal mucosae
S. Takami (2004)
10.2500/ajra.2013.27.3898
Olfactory Disorders
Alan D Gaines (2013)
10.1093/CHEMSE/27.7.623
Biopsies of human olfactory epithelium.
B. Jafek (2002)
10.1093/chemse/bjr063
Aquaporin pathways and mucin secretion of Bowman's glands might protect the olfactory mucosa.
T. T. Solbu (2012)
10.1055/s-0028-1124025
The olfactory system and its disorders.
R. Doty (2009)
10.1016/J.BIOMATERIALS.2005.03.016
Chitosan: a versatile biopolymer for orthopaedic tissue-engineering.
A. Di Martino (2005)
10.1016/j.neuron.2011.08.030
All in a Sniff: Olfaction as a Model for Active Sensing
M. Wachowiak (2011)
Olfactory mucosal findings and clinical course in patients with olfactory disorders following upper respiratory viral infection.
M. Yamagishi (1994)
10.1002/(SICI)1096-9861(19960916)373:2<240::AID-CNE7>3.0.CO;2-3
Differential adhesion and the initial assembly of the mammalian olfactory nerve
J. Whitesides (1996)
10.1080/21691401.2019.1579732
Chitosan-hyaluronan: promotion of mucociliary differentiation of respiratory epithelial cells and development of olfactory receptor neurons
T. Huang (2019)
10.1016/j.cmet.2017.06.015
The Sense of Smell Impacts Metabolic Health and Obesity.
C. Riera (2017)
10.1016/j.neuron.2011.09.009
p63 Regulates Olfactory Stem Cell Self-Renewal and Differentiation
R. Fletcher (2011)
10.1016/j.actbio.2009.08.031
Increased mucociliary differentiation of human respiratory epithelial cells on hyaluronan-derivative membranes.
T. Huang (2010)
10.2500/ajra.2017.31.4456
Promotion of Olfactory Receptor Neuron Differentiation of Olfactory Neuroepithelial Cells by Using Chitosan Solution
Sheng-Tien Li (2017)
10.1371/journal.ppat.1002986
A Heparan-Dependent Herpesvirus Targets the Olfactory Neuroepithelium for Host Entry
Ricardo Milho (2012)
10.1002/1097-4636(200011)52:2<285::AID-JBM7>3.0.CO;2-G
Studies on nerve cell affinity of chitosan-derived materials.
G. Hai-peng (2000)
10.1016/j.vaccine.2011.04.112
Pharmaceutical and immunological evaluation of mucoadhesive nanoparticles based delivery system(s) administered intranasally.
S. Mangal (2011)
[Treatment of disturbances of smell by means of chondroitin sulfate].
M. Kubo (1961)
10.1038/bjc.2014.232
Exogenous administration of protease-resistant, non-matrix-binding IGFBP-2 inhibits tumour growth in a murine model of breast cancer
C-L Soh (2014)
10.1177/000348949410300404
Olfactory Mucosa of Patients with Olfactory Disturbance following Head Trauma
M. Yamagishi (1994)
10.1210/EDRV.22.6.0452
Distinct and overlapping functions of insulin and IGF-I receptors.
J. Nakae (2001)
10.1210/ER.2001-0033
Cellular actions of the insulin-like growth factor binding proteins.
S. Firth (2002)
10.1023/B:PHAM.0000016249.52831.a5
Uptake and Cytotoxicity of Chitosan Molecules and Nanoparticles: Effects of Molecular Weight and Degree of Deacetylation
M. Huang (2004)
10.1186/2051-4190-24-12
The emerging role of insulin-like growth factors in testis development and function
R. Griffeth (2014)
10.1016/j.matbio.2015.02.003
Proteoglycan form and function: A comprehensive nomenclature of proteoglycans
R. Iozzo (2015)
10.1021/bm301222f
Mucin multilayers assembled through sugar-lectin interactions.
T. Crouzier (2012)



Semantic Scholar Logo Some data provided by SemanticScholar