Autophagy activation ameliorates the fibrosis of trabecular meshwork cells induced by TGFβ2 through the promotion of fibrotic proteins degradation.
Autophagy
/ genetics
Trabecular Meshwork
/ metabolism
Transforming Growth Factor beta2
/ metabolism
Sirolimus
/ pharmacology
Fibrosis
Humans
Animals
Proteolysis
Everolimus
/ pharmacology
Cells, Cultured
Glaucoma
/ pathology
Gene Expression
/ genetics
Smad3 Protein
/ metabolism
Signal Transduction
Chloroquine
/ pharmacology
Intraocular Pressure
Autophagy
Fibrosis
Rapamycin
Smad3
TGFβ2
Trabecular meshwork cells
Journal
Human cell
ISSN: 1749-0774
Titre abrégé: Hum Cell
Pays: Japan
ID NLM: 8912329
Informations de publication
Date de publication:
22 Oct 2024
22 Oct 2024
Historique:
received:
12
03
2024
accepted:
02
09
2024
medline:
22
10
2024
pubmed:
22
10
2024
entrez:
22
10
2024
Statut:
epublish
Résumé
The level of transforming growth factor-beta2 (TGFβ2) is elevated in aqueous humor of partial glaucoma patients, and induced trabecular meshwork (TM) fibrosis, which could cause TM cells dysfunction and lead to intraocular pressure (IOP) elevation. Autophagy is a dynamic process of bulk degradation of organelles and proteins under stress condition, while its functions in fibrotic development remain controversial. Meanwhile, it is still unclear if activation of autophagy could ameliorate TGFβ2-induced fibrosis in TM cells. In this study, we demonstrated that autophagy activation with Rapamycin or Everolimus could ameliorate TM fibrosis induced by TGFβ2. We also proved that activation of autophagy may decrease TM cells fibrosis and reduce elevated IOP induced by TGFβ2 in vivo, while Rapamycin or Everolimus has no effect on TGFβ/Smad3 pathway activity and fibrotic genes expression. However, when Chloroquine phosphate blocks autophagy-lysosome pathway, the protective effect of Rapamycin or Everolimus on fibrosis was weakened. We established that autophagy activation ameliorates TM fibrosis through promoting fibrotic proteins degradation.
Identifiants
pubmed: 39436499
doi: 10.1007/s13577-024-01141-3
pii: 10.1007/s13577-024-01141-3
doi:
Substances chimiques
Transforming Growth Factor beta2
0
Sirolimus
W36ZG6FT64
Everolimus
9HW64Q8G6G
Smad3 Protein
0
Chloroquine
886U3H6UFF
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
4Subventions
Organisme : National Natural Science Foundation of China
ID : U1904166
Organisme : Henan Medical Science and technology research plan
ID : SBGJ2018072
Informations de copyright
© 2024. The Author(s) under exclusive licence to Japan Human Cell Society.
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