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(1) To evaluate the association between expression of α-smooth muscle actin (α-SMA) in proliferative vitreoretinopathy (PVR) and the pathological grading of PVR, and the effect of platelet-derived growth factor (PDGF) on the expression of α-SMA by human retinal pigment epithelial (RPE) cells. (2) To investigate the potential induction of PDGF on the proliferation and migration of human RPE cells as well as the signaling pathways responsible.We immunohistochemically investigated the expression of α-SMA in PVR. To further investigate the effect of PDGF and the downstream signaling, exogenous PDGF-BB and signaling inhibitors were added to cultured human RPE cells. The MTT method was performed to detected cell proliferation, while cell migration was also measured.α-SMA expression was positively correlated with the pathological grading of PVR. PDGF-BB could stimulate the proliferation and migration of cultured RPE cells through the participation of mitogen-activated protein kinase. In addition, PDGF induced α-SMA expression. The promotion of proliferate/migration and α-SMA expression by PDGF-BB was enhanced by the presence of serum.PDGF and α-SMA are 2 potential therapeutic targets for the treatment of PVR.

The aim of present work was to elucidate the role of actin-depolymerizing factor (ADF), an important regulator of actin cytoskeleton, in the oxidized low-density lipoprotein (ox-LDL)-induced blood–brain barrier (BBB) disruption. The primary mouse brain microvascular endothelial cells (MBMECs) were exposed to ox-LDL. Treatment with LDL served as control. It was found that ADF mRNA level and protein expression were decreased when exposed to ox-LDL in MBMECs. Then, we investigated the influence of ADF overexpression on ox-LDL-treated MBMECs. Structurally, overexpression of ADF inhibited ox-LDL-induced F-actin formation. Functionally, overexpression of ADF attenuated ox-LDL-induced disruption of endothelial barrier marked by restoration of transendothelial electrical resistance, permeability of Evans Blue and expression of tight junction-associated proteins including ZO-1 and occludin, and blocked ox-LDL-induced oxidative stress marked by inhibition of reactive oxygen species (ROS) formation and activity of NADPH oxidase and Nox2 expression. However, overexpression of ADF in control cells had no significant effect on endothelial permeability and ROS formation. In conclusion, overexpression of ADF blocks ox-LDL-induced disruption of endothelial barrier. In addition, siRNA-mediated downregulation of ADF expression aggravated ox-LDL-induced disruption of endothelial barrier and ROS formation. These findings identify ADF as a key signaling molecule in the regulation of BBB integrity and suggest that ADF might be used as a target to modulate diseases accompanied by ox-LDL-induced BBB compromise.

Background Atherosclerosis is a chronic degenerative disease of the arteries and is thought to be one of the most common causes of death globally. In recent years, the functions of adventitial fibroblasts in the development of atherosclerosis and tissue repair have gained increased interests. LPS can increase the morbidity and mortality of atherosclerosis-associated cardiovascular disease. Although LPS increases neointimal via TLR4 activation has been reported, how LPS augments atherogenesis through acting on adventitial fibroblasts is still unknown. Here we explored lipid deposition within adventitial fibroblasts mediated by lipopolysaccharide (LPS) to imitate inflammatory conditions. Results In our study, LPS enhanced lipid deposition by the up-regulated expression of adipose differentiation-related protein (ADRP) as the silencing of ADRP abrogated lipid deposition in LPS-activated adventitial fibroblasts. In addition, pre-treatment with anti-Toll-like receptor 4 (TLR4) antibody diminished the LPS-induced lipid deposition and ADRP expression. Moreover, LPS induced translocation of nuclear factor-κB (NF-κB), which could markedly up-regulate lipid deposition as pre-treatment with the NF-κB inhibitor, PDTC, significantly reduced lipid droplets. In addition, the lowering lipid accumulation was accompanied with the decreased ADRP expression. Furthermore, LPS-induced adventitial fibroblasts secreted more monocyte chemoattractant protein (MCP-1), compared with transforming growth factor-β1 (TGF-β1). Conclusions Taken together, these results suggest that LPS promotes lipid accumulation via the up-regulation of ADRP expression through TLR4 activated downstream of NF-κB in adventitial fibroblasts. Increased levels of MCP-1 released from LPS-activated adventitial fibroblasts and lipid accumulation may accelerate monocytes recruitment and lipid-laden macrophage foam cells formation. Here, our study provides a new explanation as to how bacterial infection contributes to the pathological process of atherosclerosis.