Role of the autotaxin-lysophosphatidic acid axis in glaucoma, aqueous humor drainage and fibrogenic activity.
Animals
Aqueous Humor
/ metabolism
Collagen Type I
/ metabolism
Connective Tissue Growth Factor
/ metabolism
Drainage
/ methods
Female
Fibronectins
/ metabolism
Glaucoma
/ metabolism
Humans
Intraocular Pressure
/ physiology
Lysophospholipids
/ metabolism
Male
Mice
Mice, Inbred C57BL
NF-kappa B
/ metabolism
Ocular Hypertension
/ metabolism
Phosphoric Diester Hydrolases
/ metabolism
Smad3 Protein
/ metabolism
Trabecular Meshwork
/ metabolism
Aqueous humor
Autotaxin
Glaucoma
Intraocular pressure
Trabecular meshwork
Journal
Biochimica et biophysica acta. Molecular basis of disease
ISSN: 1879-260X
Titre abrégé: Biochim Biophys Acta Mol Basis Dis
Pays: Netherlands
ID NLM: 101731730
Informations de publication
Date de publication:
01 01 2020
01 01 2020
Historique:
received:
22
05
2019
revised:
27
08
2019
accepted:
16
09
2019
pubmed:
28
10
2019
medline:
8
7
2020
entrez:
25
10
2019
Statut:
ppublish
Résumé
Ocular hypertension due to impaired aqueous humor (AH) drainage through the trabecular meshwork (TM) is a major risk factor for glaucoma, a leading cause of irreversible blindness. However, the etiology of ocular hypertension remains unclear. Although autotaxin, a secreted lysophospholipase D and its catalytic product lysophosphatidic acid (LPA) have been shown to modulate AH drainage through TM, we do not have a complete understanding of their role and regulation in glaucoma patients, TM and AH outflow. This study reports a significant increase in the levels of autotaxin, lysophosphatidylcholine (LPC), LPA and connective tissue growth factor (CTGF) in the AH of Caucasian and African American open angle glaucoma patients relative to age-matched non-glaucoma patients. Treatment of human TM cells with dexamethasone, tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) increased the levels of autotaxin protein, a response that was mitigated by inhibitors of glucocorticoid receptor, NF-kB and SMAD3. Dexamethasone, TNF-α, IL-1β and LPC treatment of TM cells also led to an increase in the levels of CTGF, fibronectin and collagen type 1 in an autotaxin dependent manner. Additionally, in perfused enucleated mouse eyes, autotaxin and LPC were noted to decrease, while inhibition of autotaxin was increased aqueous outflow through the TM. Taken together, these results provide additional evidence for dysregulation of the autotaxin-LPA axis in the AH of glaucoma patients, reveal molecular insights into the regulation of autotaxin expression in TM cells and the consequences of autotaxin inhibitors in suppressing the fibrogenic response and resistance to AH outflow through the TM.
Identifiants
pubmed: 31648019
pii: S0925-4439(19)30283-2
doi: 10.1016/j.bbadis.2019.165560
pmc: PMC6863611
mid: NIHMS1542413
pii:
doi:
Substances chimiques
Collagen Type I
0
Fibronectins
0
Lysophospholipids
0
NF-kappa B
0
Smad3 Protein
0
Connective Tissue Growth Factor
139568-91-5
Phosphoric Diester Hydrolases
EC 3.1.4.-
alkylglycerophosphoethanolamine phosphodiesterase
EC 3.1.4.39
lysophosphatidic acid
PG6M3969SG
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
165560Subventions
Organisme : NEI NIH HHS
ID : R01 EY018590
Pays : United States
Informations de copyright
Copyright © 2019 Elsevier B.V. All rights reserved.
Références
N Engl J Med. 2009 Mar 12;360(11):1113-24
pubmed: 19279343
PLoS One. 2012;7(8):e42627
pubmed: 22916143
Retina. 2016 Dec;36(12):2311-2318
pubmed: 27648638
Development. 2015 Apr 15;142(8):1390-5
pubmed: 25852197
Invest Ophthalmol Vis Sci. 2004 Jul;45(7):2263-71
pubmed: 15223804
Front Med (Lausanne). 2018 Jun 13;5:180
pubmed: 29951481
J Pharmacol Exp Ther. 2017 Jan;360(1):1-13
pubmed: 27754931
Cell. 2012 Aug 17;150(4):780-91
pubmed: 22863277
Invest Ophthalmol Vis Sci. 2018 Feb 1;59(2):693-701
pubmed: 29392315
Invest Ophthalmol Vis Sci. 2018 Apr 1;59(5):1969-1984
pubmed: 29677358
Mol Med Rep. 2015 Feb;11(2):1384-90
pubmed: 25351602
Expert Opin Pharmacother. 2017 Oct;18(15):1669-1673
pubmed: 28893104
J Glaucoma. 2018 Jan;27(1):7-15
pubmed: 29194198
Drugs Today (Barc). 2018 Aug;54(8):467-478
pubmed: 30209441
Invest Ophthalmol Vis Sci. 1997 Jan;38(1):83-91
pubmed: 9008633
Invest Ophthalmol Vis Sci. 2010 Feb;51(2):903-6
pubmed: 19737888
Exp Eye Res. 2017 May;158:23-32
pubmed: 27593914
J Lipid Res. 2014 Jul;55(7):1192-214
pubmed: 24643338
JCI Insight. 2018 Mar 22;3(6):
pubmed: 29563341
Exp Eye Res. 2009 Dec;89(6):980-8
pubmed: 19715693
Matrix Biol. 2014 Jul;37:174-82
pubmed: 24727033
J Cell Physiol. 2014 Jul;229(7):927-42
pubmed: 24318513
Am J Pathol. 2015 Feb;185(2):496-512
pubmed: 25499974
Prog Retin Eye Res. 2017 Jan;56:58-83
pubmed: 27666015
Exp Cell Res. 2015 May 1;333(2):171-7
pubmed: 25499971
Sci Rep. 2018 Jul 27;8(1):11304
pubmed: 30054520
Sci Signal. 2017 Apr 11;10(474):null
pubmed: 28400537
Prog Mol Biol Transl Sci. 2015;134:301-14
pubmed: 26310162
Invest Ophthalmol Vis Sci. 2018 Jan 1;59(1):21-30
pubmed: 29305605
Exp Eye Res. 2009 Apr;88(4):752-9
pubmed: 18977348
Prog Retin Eye Res. 2017 Mar;57:108-133
pubmed: 28028002
Prog Lipid Res. 2007 Mar;46(2):145-60
pubmed: 17459484
Genes Dev. 2008 Jul 15;22(14):1962-71
pubmed: 18579750
JAMA. 2014 May 14;311(18):1901-11
pubmed: 24825645
Eur J Pharmacol. 2015 Oct 15;765:228-33
pubmed: 26297977
J Ocul Pharmacol Ther. 2014 Mar-Apr;30(2-3):181-90
pubmed: 24283588
J Biochem. 2015 Feb;157(2):81-9
pubmed: 25500504
Biochem Pharmacol. 2019 Jun;164:74-81
pubmed: 30928673
Am J Physiol Cell Physiol. 2010 Mar;298(3):C749-63
pubmed: 19940066
Am J Respir Cell Mol Biol. 2012 Nov;47(5):563-5
pubmed: 23125419
J Med Chem. 2016 Jun 23;59(12):5604-21
pubmed: 26745766
J Cell Sci Suppl. 1994;18:127-31
pubmed: 7883787
Biochem Biophys Res Commun. 2014 Jan 17;443(3):917-23
pubmed: 24380865
J Cell Biol. 2002 Jul 22;158(2):227-33
pubmed: 12119361
Curr Opin Ophthalmol. 2012 Mar;23(2):135-43
pubmed: 22262082
Biochimie. 2015 Jun;113:59-68
pubmed: 25843665
PLoS One. 2016 Mar 07;11(3):e0150694
pubmed: 26949939