Sequential Wnt Agonist Then Antagonist Treatment Accelerates Tissue Repair and Minimizes Fibrosis.
Cellular Physiology
Mathematical Biosciences
Molecular Physiology
Pathophysiology
Physiology
Journal
iScience
ISSN: 2589-0042
Titre abrégé: iScience
Pays: United States
ID NLM: 101724038
Informations de publication
Date de publication:
22 May 2020
22 May 2020
Historique:
received:
02
10
2019
revised:
15
03
2020
accepted:
05
04
2020
pubmed:
28
4
2020
medline:
28
4
2020
entrez:
28
4
2020
Statut:
ppublish
Résumé
Tissue fibrosis compromises organ function and occurs as a potential long-term outcome in response to acute tissue injuries. Currently, lack of mechanistic understanding prevents effective prevention and treatment of the progression from acute injury to fibrosis. Here, we combined quantitative experimental studies with a mouse kidney injury model and a computational approach to determine how the physiological consequences are determined by the severity of ischemia injury and to identify how to manipulate Wnt signaling to accelerate repair of ischemic tissue damage while minimizing fibrosis. The study reveals that memory of prior injury contributes to fibrosis progression and ischemic preconditioning reduces the risk of death but increases the risk of fibrosis. Furthermore, we validated the prediction that sequential combination therapy of initial treatment with a Wnt agonist followed by treatment with a Wnt antagonist can reduce both the risk of death and fibrosis in response to acute injuries.
Identifiants
pubmed: 32339988
pii: S2589-0042(20)30232-7
doi: 10.1016/j.isci.2020.101047
pmc: PMC7186527
pii:
doi:
Types de publication
Journal Article
Langues
eng
Pagination
101047Subventions
Organisme : NIDDK NIH HHS
ID : R01 DK064005
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR001857
Pays : United States
Organisme : NIDDK NIH HHS
ID : K01 DK116816
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK106049
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK119232
Pays : United States
Informations de copyright
Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Interests The authors declare no conflict of interest.
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