Effect of bradykinin on TGF-β1-induced retinal pigment epithelial cell proliferation and extracellular matrix secretion.
BACKGROUND
To evaluate the effect of bradykinin (BK) on TGF-β1-induced retinal pigment epithelial (RPE) cell proliferation and extracellular matrix secretion and to elucidate the relationship between BK and the Erk/Akt signaling pathway.


METHODS
The effects of BK on TGF-β1-induced RPE cell proliferation were examined via CCK-8 assay. Cell culture supernatant collagen I concentrations were measured via ELISA. Fibronectin (Fn), matrix metalloproteinase-2 (MMP-2) and MMP-9 mRNA and protein expression levels were measured via q-PCR and Western blotting, respectively. Changes in Akt/Erk phosphorylation induced by BK and HOE-140 were evaluated via Western blotting.


RESULTS
TGF-β1 stimulated ARPE-19 cell proliferation, which was inhibited by BK, whose effects were inhibited by HOE-140. BK inhibited TGF-β1-induced collagen I, Fn and MMP-2 secretion in RPE cells, and these effects were inhibited by HOE-140. BK also inhibited TGF-β1-induced Akt phosphorylation in RPE cells, and these effects were blocked by HOE-140. BK had no significant effect on Erk-mediated signaling.


CONCLUSIONS
The findings from this study indicate that BK could be novel therapeutic targets for the treatment of PVR.
Department of Ophthalmology, Shanghai Tenth People's Hospital, Tongji University, School of Medicine, Shanghai, China.
Wenting
W
Cai
Nanchang University, Jiangxi, China.
Qingquan
Q
Wei
Department of Ophthalmology, Shanghai Tenth People's Hospital, Tongji University, School of Medicine, Shanghai, China.
Qingyu
Q
Liu
Department of Ophthalmology, Shanghai Tenth People's Hospital, Tongji University, School of Medicine, Shanghai, China.
Chengda
C
Ren
Department of Ophthalmology, Shanghai Tenth People's Hospital, Tongji University, School of Medicine, Shanghai, China.
Junling
J
Liu
Department of Ophthalmology, Shanghai Tenth People's Hospital, Tongji University, School of Medicine, Shanghai, China.
Ruiling
R
Zhang
Department of Ophthalmology, Shanghai Tenth People's Hospital, Tongji University, School of Medicine, Shanghai, China.
Mengmei
M
He
Department of Ophthalmology, Shanghai Tenth People's Hospital, Tongji University, School of Medicine, Shanghai, China.
Qianyi
Q
Wang
Department of Ophthalmology, The 180th Hospital of Chinese People's Liberation Army, Quanzhou, Fujian province, China. dyrdyr518@163.com.
Yaru
Y
Du
Department of Ophthalmology, Shanghai Tenth People's Hospital, Tongji University, School of Medicine, Shanghai, China. dryujing@aliyun.com.
Jing
J
Yu
D015153:Blotting, Western; D001920:Bradykinin / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D024042:Collagen Type I / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005109:Extracellular Matrix / Q000187:drug effects* / Q000378:metabolism; D005353:Fibronectins / Q000378:metabolism; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D055213:Retinal Pigment Epithelium / Q000166:cytology* / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects; D053773:Transforming Growth Factor beta1; D014665:Vasodilator Agents / Q000494:pharmacology*; D018630:Vitreoretinopathy, Proliferative / Q000188:drug therapy
D024042:Collagen Type I; D005353:Fibronectins; D012333:RNA, Messenger; D053773:Transforming Growth Factor beta1; D014665:Vasodilator Agents; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D001920:Bradykinin
Bradykinin; Extracellular matrix; Proliferative vitreoretinopathy; Retinal pigment epithelium; Transforming growth factor-β1