Triamcinolone acetonide modulates TGF‑β2‑induced angiogenic and tissue‑remodeling effects in cultured human retinal pigment epithelial cells

Abstract

Transforming growth factor-β2 (TGF-β2) has been implicated in the pathogenesis of proliferative vitreoretinopathy (PVr) and proliferative diabetic retinopathy (Pdr), due to its ability to stimulate the overproduction of pro-angiogenic 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 TGF-β2-driven 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 r-50 human rPe cell line was treated with Ta in the presence of TGF-β2, followed by analyses of cell viability and contraction using cell viability and collagen gel contrac-tion assays. VeGF mrna expression and protein production were measured using reverse transcription-quantitative Pcr and eliSa, respectively. The phosphorylation status of signaling mediators and the protein expression of type i collagen (col1a1), α-smooth muscle actin (α-SMa), and ecM-remodeling enzymes, including MMP-2 and MMP-9, were analyzed using western blotting. The gelatinolytic activity of MMPs was detected using gelatin zymography. Ta treatment exhibited no prominent cytotoxicity but markedly antagonized TGF-β2-induced cytostatic effects on rPe cell viability and TGF-β2-enhanced contractility in collagen gels. in the context of TGF-β2-related signaling, TA significantly attenuated TGF-β2-elicited Smad2, extracellular-regulated kinase (erK)1/2 and p38 mitogen-activated protein kinase (MaPK) phosphorylation. Moreover, Ta markedly mitigated TGF-β2-induced VeGF upregulation through ablation of p38 signaling activity. Ta also partially attenuated TGF-β2-elicted expression of col1a1, α-SMa, MMP-2, and MMP-9, but only suppressed TGF-β2-induced MMP-9 gelatinolytic activity. Mechanistically, the MeK/erK signaling pathway may have a critical role in the TGF-β2-induced upregulation of col1a1, α-SMa and MMP-9. in conclusion, Ta may be considered a useful therapeutic agent for treating TGF-β2-associated intraocular angiogenesis and tissue remodeling, the underlying mechanism of which may involve the erK and p38 MaPK signaling pathways.

Role of Autotaxin in High Glucose-Induced Human ARPE-19 Cells

“…ICC showed significantly increased expression levels of COL1A1 ( Figure 8 D); αSMA ( Figure 9 D); and F-actin ( Figure 10 ) in the HG group. Our results suggest that fibrogenic activity and cytoskeletal reorganization are increased in PDR, which is indicative of pathological angiogenesis [ 50 , 51 , 52 , 53 , 54 , 55 , 56 ]. In addition, HG induced significant upregulations of TGF-β1, TGF-β2, and TGF-β3 levels in ARPE-19 cells ( Figure 11 ), whereas the TGF-βi level did not differ significantly among the three groups ( Figure S6 ).…”

Effect of Oral Prednisone on the Prevention and Management of Proliferative Vitreoretinopathy After Open-Globe Injury

“…16,17 In addition, the clinical use of triamcinolone in the prevention of PVR is attributed to its antiangiogenic properties. Although the mechanism has not been completely elucidated, Hsiao et al 18 found that transforming growth factor-β2, a stimulant for the production of proangiogenesis factors, is attenuated in cultured human retinal epithelial cells with the use of triamcinolone. 18 In a study of triamcinolone’s safety, Veritti et al 13 reported that although triamcinolone was associated with some adverse ocular events, such as ocular hypertension, steroid-induced cataracts, and infection, it was an effective drug for various retinal and choroidal diseases.…”

Bone morphogenetic protein-6 suppresses TGF-β2-induced epithelial-mesenchymal transition in retinal pigment epithelium

“…A study by Pao et al [21] suggested that the overexpression of miR-4516 suppresses TGF-β 2 -induced EMT in a PVR model, and its role in PVR depends on ERK signalling. Research has also suggested that inhibition of ERK signalling pathways suppresses proliferation in human RPE cells [22] . Our study results were aligned with their findings.…”