Galectin-3 levels are elevated following nintedanib treatment.
galectin-3
idiopathic pulmonary fibrosis
in vivo models
nintedanib
signal transducer and activator of transcription 3 (STAT3)
Journal
Therapeutic advances in chronic disease
ISSN: 2040-6223
Titre abrégé: Ther Adv Chronic Dis
Pays: United States
ID NLM: 101532140
Informations de publication
Date de publication:
2020
2020
Historique:
received:
19
07
2020
accepted:
02
10
2020
entrez:
12
3
2021
pubmed:
13
3
2021
medline:
13
3
2021
Statut:
epublish
Résumé
Idiopathic pulmonary fibrosis (IPF) is a common and severe form of pulmonary fibrosis. Nintedanib, a triple angiokinase inhibitor, is approved for treating IPF. Galectin 3 (Gal-3) activates a variety of profibrotic processes. Currently, the Gal-3 inhibitor TD139 is being tested in phase II clinical trials. Since this treatment is given 'on top' of nintedanib, it is important to estimate its effect on Gal-3 levels. Therefore, we evaluated the impact of nintedanib on Gal-3 expression using both Gal-3 levels were evaluated in IPF and control tissue samples, primary human lung fibroblasts (HLFs) following nintedanib treatment (10-100 nM, quantitative polymerase chain reaction), and in a silica-induced fibrosis mouse model with/without nintedanib (0.021-0.21 mg/kg) by immunohistochemistry. In addition, Gal-3 levels were analyzed in serum samples from 41 patients with interstitial lung disease patients with/without nintedanib treatment by ELISA. Nintedanib addition to HLFs resulted in significant elevations in Gal-3, phospho-signal transducer and activator of transcription 3 (pSTAT3), as well as IL-8 mRNA levels ( Nintedanib elevates Gal-3 levels in both experimental models, along with patient samples. These findings highlight the possibility of using combined inhibition therapy for patients with IPF.
Sections du résumé
BACKGROUND AND AIMS
OBJECTIVE
Idiopathic pulmonary fibrosis (IPF) is a common and severe form of pulmonary fibrosis. Nintedanib, a triple angiokinase inhibitor, is approved for treating IPF. Galectin 3 (Gal-3) activates a variety of profibrotic processes. Currently, the Gal-3 inhibitor TD139 is being tested in phase II clinical trials. Since this treatment is given 'on top' of nintedanib, it is important to estimate its effect on Gal-3 levels. Therefore, we evaluated the impact of nintedanib on Gal-3 expression using both
METHODS
METHODS
Gal-3 levels were evaluated in IPF and control tissue samples, primary human lung fibroblasts (HLFs) following nintedanib treatment (10-100 nM, quantitative polymerase chain reaction), and in a silica-induced fibrosis mouse model with/without nintedanib (0.021-0.21 mg/kg) by immunohistochemistry. In addition, Gal-3 levels were analyzed in serum samples from 41 patients with interstitial lung disease patients with/without nintedanib treatment by ELISA.
RESULTS
RESULTS
Nintedanib addition to HLFs resulted in significant elevations in Gal-3, phospho-signal transducer and activator of transcription 3 (pSTAT3), as well as IL-8 mRNA levels (
CONCLUSION
CONCLUSIONS
Nintedanib elevates Gal-3 levels in both experimental models, along with patient samples. These findings highlight the possibility of using combined inhibition therapy for patients with IPF.
Identifiants
pubmed: 33708368
doi: 10.1177/2040622320968412
pii: 10.1177_2040622320968412
pmc: PMC7907712
doi:
Types de publication
Journal Article
Langues
eng
Pagination
2040622320968412Informations de copyright
© The Author(s), 2020.
Déclaration de conflit d'intérêts
Conflict of interest statement: The authors declare that there is no conflict of interest.
Références
Immunol Rev. 2009 Jul;230(1):160-71
pubmed: 19594635
Turk Patoloji Derg. 2012;28(1):1-10
pubmed: 22207425
Eur Respir J. 2019 Sep 19;54(3):
pubmed: 31285305
Pulm Pharmacol Ther. 2020 Aug;63:101933
pubmed: 32750409
Sci Rep. 2015 Nov 06;5:16082
pubmed: 26542452
Respir Res. 2017 Jun 19;18(1):122
pubmed: 28629363
Am J Respir Crit Care Med. 2016 Jul 1;194(1):77-83
pubmed: 26771117
J Pathol. 2016 Aug;239(4):411-25
pubmed: 27135434
Cell Biol Int. 2018 Sep;42(10):1292-1299
pubmed: 29885023
Am Heart J. 2014 Jun;167(6):853-60.e4
pubmed: 24890535
Cancer Res. 2008 Jun 15;68(12):4774-82
pubmed: 18559524
Respir Res. 2018 Oct 19;19(1):203
pubmed: 30340638
J Pharmacol Exp Ther. 2014 May;349(2):209-20
pubmed: 24556663
Allergol Int. 2007 Mar;56(1):57-65
pubmed: 17259811
Int J Mol Med. 2018 Feb;41(2):599-614
pubmed: 29207027
J Am Coll Cardiol. 2012 Oct 2;60(14):1249-56
pubmed: 22939561
JCI Insight. 2019 Nov 14;4(22):
pubmed: 31600171
Proc Natl Acad Sci U S A. 1996 Jun 25;93(13):6737-42
pubmed: 8692888
J Pathol. 1996 Jul;179(3):309-16
pubmed: 8774488
Thorax. 2006 Nov;61(11):980-5
pubmed: 16844727
N Engl J Med. 2011 Sep 22;365(12):1079-87
pubmed: 21992121
Mol Cancer Ther. 2012 Oct;11(10):2254-64
pubmed: 22891040
Biochemistry. 1994 Nov 29;33(47):14109-14
pubmed: 7947821
Sci Rep. 2017 Dec 4;7(1):16878
pubmed: 29203879
N Engl J Med. 2018 May 10;378(19):1811-1823
pubmed: 29742380
Exp Cell Res. 2010 May 1;316(8):1324-31
pubmed: 20211171
Am J Respir Crit Care Med. 2012 Mar 1;185(5):537-46
pubmed: 22095546
N Engl J Med. 2014 May 29;370(22):2071-82
pubmed: 24836310
J Pharmacol Exp Ther. 2014 Nov;351(2):336-43
pubmed: 25194021
Breast Cancer Res Treat. 2014 May;145(1):5-22
pubmed: 24668500
J Immunol Res. 2020 Feb 14;2020:5284728
pubmed: 32149158
Am J Nephrol. 2016;43(5):305-17
pubmed: 27166158
Immunol Lett. 1994 Oct;42(3):113-6
pubmed: 7890309
Transplantation. 2012 Mar 15;93(5):477-84
pubmed: 22306573
Exp Mol Med. 2017 Aug 11;49(8):e366
pubmed: 28798401
Clin Sci (Lond). 2017 Jul 24;131(16):2125-2143
pubmed: 28646122
Mol Carcinog. 2017 Jan;56(1):62-74
pubmed: 26859229
Eur Respir J. 2015 May;45(5):1434-45
pubmed: 25745043
Sci Rep. 2016 Dec 16;6:39112
pubmed: 27982117
Ann Med. 2011 Feb;43(1):60-8
pubmed: 21189092
J Cell Sci. 2015 Jul 1;128(13):2213-9
pubmed: 26092931
N Engl J Med. 2018 Aug 23;379(8):797-798
pubmed: 30134133
Theranostics. 2017 Sep 26;7(17):4255-4275
pubmed: 29158824