Triamcinolone acetonide modulates TGFß2induced angiogenic and tissueremodeling effects in cultured human retinal pigment epithelial cells.
Mol Med Rep
; 24(5)2021 11.
Article
in En
| MEDLINE
| ID: mdl-34523693
Transforming growth factorß2 (TGFß2) has been implicated in the pathogenesis of proliferative vitreoretinopathy (PVR) and proliferative diabetic retinopathy (PDR), due to its ability to stimulate the overproduction of proangiogenic factors, such as vascular endothelial growth factor (VEGF), and remodeling of the extracellular matrix (ECM). Although intravitreal triamcinolone acetonide (TA) is clinically useful in the treatment of PVR and PDR, its molecular mechanism has yet to be fully elucidated. The present study investigated whether TA treatment altered TGFß2driven biological effects on the behavior of cultured human retinal pigment epithelial (RPE) cells, in order to determine which signaling pathway may be essential for the pharmacological action of TA. The R50 human RPE cell line was treated with TA in the presence of TGFß2, followed by analyses of cell viability and contraction using cell viability and collagen gel contraction assays. VEGF mRNA expression and protein production were measured using reverse transcriptionquantitative PCR and ELISA, respectively. The phosphorylation status of signaling mediators and the protein expression of type I collagen (COL1A1), αsmooth muscle actin (αSMA), and ECMremodeling enzymes, including MMP2 and MMP9, were analyzed using western blotting. The gelatinolytic activity of MMPs was detected using gelatin zymography. TA treatment exhibited no prominent cytotoxicity but markedly antagonized TGFß2induced cytostatic effects on RPE cell viability and TGFß2enhanced contractility in collagen gels. In the context of TGFß2related signaling, TA significantly attenuated TGFß2elicited Smad2, extracellularregulated kinase (ERK)1/2 and p38 mitogenactivated protein kinase (MAPK) phosphorylation. Moreover, TA markedly mitigated TGFß2induced VEGF upregulation through ablation of p38 signaling activity. TA also partially attenuated TGFß2elicted expression of COL1A1, αSMA, MMP2, and MMP9, but only suppressed TGFß2induced MMP9 gelatinolytic activity. Mechanistically, the MEK/ERK signaling pathway may have a critical role in the TGFß2induced upregulation of COL1A1, αSMA and MMP9. In conclusion, TA may be considered a useful therapeutic agent for treating TGFß2associated intraocular angiogenesis and tissue remodeling, the underlying mechanism of which may involve the ERK and p38 MAPK signaling pathways.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Triamcinolone Acetonide
/
Retinal Pigment Epithelium
Limits:
Humans
Language:
En
Journal:
Mol Med Rep
Year:
2021
Document type:
Article
Country of publication: