2. Academic Validation
  3. Bromfenac Inhibits TGF-β1-Induced Fibrotic Effects in Human Pterygium and Conjunctival Fibroblasts

Bromfenac Inhibits TGF-β1-Induced Fibrotic Effects in Human Pterygium and Conjunctival Fibroblasts

  • Invest Ophthalmol Vis Sci. 2019 Mar 1;60(4):1156-1164. doi: 10.1167/iovs.18-24743.
Kailin Chen 1 2,  Kairan Lai 1 2,  Xiaobo Zhang 1 2,  Zhenwei Qin 1 2,  Qiuli Fu 1 2,  Chenqi Luo 1 2,  Xiuming Jin 1 2,  Jianghua Hu 1 2,  Siyu Liu 1 2,  Ke Yao 1 2
Affiliations

Affiliations

  • 1 Eye Center, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, People's Republic of China.
  • 2 Key Laboratory of Ophthalmology of Zhejiang Province, Hangzhou, People's Republic of China.
PMID: 30908581 DOI: 10.1167/iovs.18-24743
Abstract

Purpose: Nonsteroidal anti-inflammatory drugs (NSAIDs) have shown antifibrotic effects on several diseases. The aims of the present in vitro study were to investigate the antifibrotic effects of bromfenac (a kind of NSAID) on primary human pterygium fibroblasts (HPFs) and primary human conjunctival fibroblasts (HConFs), as well as to explore the possible mechanisms of these effects.

Methods: The cells used in this study were primary HPFs and HConFs, and profibrotic activation was induced by transforming growth factor-beta1 (TGF-β1). Western blot, quantitative Real-Time PCR, and immunofluorescence (IF) assays were used to detect the effects of TGF-β1 and bromfenac on the synthesis of fibronectin (FN), type III collagen (COL3), and alpha-smooth muscle actin (α-SMA) in HPFs and HConFs; the changes of signaling pathways were detected by Western blot; cell migration ability was detected by wound healing assay; cell proliferation ability was detected by CCK-8 assay; and pharmaceutical inhibitions of the downstream signaling pathways of TGF-β1 were used to assess their possible associations with the effects of bromfenac.

Results: Bromfenac suppressed the TGF-β1-induced protein expression of FN (0.59 ± 0.07 folds, P = 0.008), COL3 (0.48 ± 0.08 folds, P = 0.001), and α-SMA (0.61 ± 0.03 folds, P = 0.008) in HPFs. Bromfenac also attenuated TGF-β1-induced cell migration (0.30 ± 0.07 folds, P < 0.001), cell proliferation (0.64 ± 0.03 folds, P = 0.002) and the expression levels of p-AKT (0.66 ± 0.08 folds, P = 0.032), p-ERK1/2 (0.69 ± 0.11 folds, P = 0.003), and p-GSK-3β-S9 (0.65 ± 0.10 folds, P = 0.002) in HPFs. PI3K/Akt Inhibitor (wortmannin) and MEK/ERK Inhibitor (U0126) reduced the TGF-β1-induced synthesis of FN, COL3, and α-SMA in HPFs. All the results were similar in HConFs.

Conclusions: Bromfenac protects against TGF-β1-induced synthesis of FN, α-SMA, and COL3 in HPFs and HConFs at least in part by inactivating the Akt and ERK pathways.

Figures
Products