Back to Search
Start Over
AR12286 Alleviates TGF-β-Related Myofibroblast Transdifferentiation and Reduces Fibrosis after Glaucoma Filtration Surgery
- Source :
- Molecules, Volume 25, Issue 19, Molecules, Vol 25, Iss 4422, p 4422 (2020)
- Publication Year :
- 2020
- Publisher :
- Multidisciplinary Digital Publishing Institute, 2020.
-
Abstract
- Scar formation can cause the failure of glaucoma filtration surgery. We investigated the effect of AR12286, a selective Rho-associated kinase inhibitor, on myofibroblast transdifferentiation and intraocular pressure assessment in rabbit glaucoma filtration surgery models. Cell migration and collagen contraction were used to demonstrate the functionality of AR12286-modulated human conjunctival fibroblasts (HConFs). Polymerase chain reaction quantitative analysis was used to determine the effect of AR12286 on the production of collagen Type 1A1 and fibronectin 1. Cell migration and collagen contraction in HConFs were activated by TGF-&beta<br />1. However, compared with the control group, rabbit models treated with AR12286 exhibited higher reduction in intraocular pressure after filtration surgery, and decreased collagen levels at the wound site in vivo. Therefore, increased &alpha<br />SMA expression in HConFs induced by TGF-&beta<br />1 could be inhibited by AR12286, and the production of Type 1A1 collagen and fibronectin 1 in TGF-&beta<br />1-treated HConFs was inhibited by AR12286. Overall, the stimulation of HConFs by TGF-&beta<br />1 was alleviated by AR12286, and this effect was mediated by the downregulation of TGF-&beta<br />receptor-related SMAD signaling pathways. In vivo results indicated that AR12286 thus improves the outcome of filtration surgery as a result of its antifibrotic action in the bleb tissue because AR12286 inhibited the TGF-&beta<br />receptor-related signaling pathway, suppressing several downstream reactions in myofibroblast transdifferentiation.
- Subjects :
- TGF-β
Pharmaceutical Science
AR12286
Article
Cell Line
Analytical Chemistry
lcsh:QD241-441
03 medical and health sciences
0302 clinical medicine
lcsh:Organic chemistry
human conjunctival fibroblast
Transforming Growth Factor beta
In vivo
Fibrosis
Drug Discovery
medicine
Animals
Humans
Bleb (cell biology)
Physical and Theoretical Chemistry
Myofibroblasts
Protein Kinase Inhibitors
030304 developmental biology
glaucoma filtration surgery
0303 health sciences
biology
Chemistry
Organic Chemistry
Transdifferentiation
Glaucoma
Cell migration
α-SMA
medicine.disease
Fibronectin
Chemistry (miscellaneous)
Cell Transdifferentiation
Filtering Surgery
030221 ophthalmology & optometry
Cancer research
biology.protein
Molecular Medicine
Rabbits
Signal transduction
Myofibroblast
SMAD
Signal Transduction
Subjects
Details
- Language :
- English
- ISSN :
- 14203049
- Database :
- OpenAIRE
- Journal :
- Molecules
- Accession number :
- edsair.doi.dedup.....c74b5f08cf5ef90236af064fbfc861c5
- Full Text :
- https://doi.org/10.3390/molecules25194422