It can affect cell proliferation by significantly inhibiting the effects of
It can affect cell proliferation by significantly inhibiting the effects of TGF-1. In addition, HOE-140, a bradykinin B2 receptor antagonist, blocked the effects of BK on TGF-1. Therefore, this study demonstrated that BK regulates TGF-1-induced RPE cell proliferation by activating the BK B2R. TGF-1 is an important regulator of ECM synthesis and degradation, as well as fibrosis [29, 30]. Connor showed that PVR patients exhibit significant increases in their vitreous fluid TGF- concentrations and that theseCai et al. BMC Ophthalmology (2016) 16:Page 8 ofincreases are directly proportional to PVR severity [31]. Baudouin noted increased TGF-1 concentrations in subretinal fluid samples that were collected during different PVR periods. These findings indicate that TGF-1 plays a role in PVR development and that inhibiting TGF-1 expression may prevent PVR development [32]. Obeta reported that TGF-1 activates Smad-dependent and Smad-independent signaling by binding TGF- receptors. The Smad-independent signaling pathways comprise the PI3K-Akt, mitogen-activated protein kinase (MAPK), and JNK/p38 pathways, as well as other pathways [33]. The extracellular signal-related kinase1/2 (Erk1/2) signaling pathway is one of the most important signaling pathways associated with MAPK activity, which can be activated via phosphorylation cascade stimulation to regulate cell proliferation and differentiation [34]. PI3K plays a role in cell proliferation and differentiation and has been shown to regulate proto-oncogene expression. PI3K/Akt (also known as protein kinase B, PKB) signaling plays an important role in cell proliferation and survival [35]. Previous studies have shown that BK increases vascular smooth muscle cell proliferation by activating the Erk signaling pathway and that BK may also play a role in collagen synthesis and secretion by inhibiting TGF–induced Akt phosphoylation [27]. In the present study, ARPE-19 cells were stimulated by TGF-1 and then treated with HOE-140 to determine the effect of BK on TGF-1-induced ECM and MMP secretion by ARPE-19 cells, elucidate the mechanism underlying this effect, and clarify the relationship between BK and Akt/MAPK (Erk1/2) signaling. We found that BK inhibited TGF-1-induced ECM deposition and MMP secretion. Moreover, TGF–induced Akt phosphorylation was also inhibited by BK. This inhibition was blocked by HOE-140, indicating that BK inhibits the effects of TGF1. The BK B2R is a G protein-coupled receptor (GPCR), and the mechanism underlying the effects of BK may involve protein-protein interactions between GPCRs and TGF- receptors. Additional in-depth studies must be performed to identify the intracellular signaling pathways and RG7666 supplier specific protein-protein interactions associated with the effects of BK. This study had some limitations. First, the KKS system is complicated. Although BK PubMed ID: is the primary determinant of KKS activity, other substances in the KKS system may also have an impact on collagen formation in RPE cells. Second, our study involved only cultured RPE PubMed ID: cells. We did not establish an animal model. Third, our study explored the effects of BK on TGF-1-induced RPE cell proliferation; however, in the process of PVR, there are many growth factors such as transforming growth factor, hepatocyte growth factor, insulin-like growth factor and so on. A variety of growth factors are involved in theprocess of PVR, cell function changes stimulated by different growth factors may lead to changes in downstream ef.

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