Fibronectin is a critical component of the extracellular matrix and alterations to its structure will influence cellular behavior. Matrix fibronectin is subjected to both mechanical and biochemical regulation. The Type III domains of fibronectin can be unfolded in response to increased cellular contractility, included or excluded from the molecule by alternative splicing mechanisms, or released from the matrix by proteolysis. Using Inflammatory Cytokine microarrays we found that the alternatively spliced fibronectin Type III domain, FnEDA, and the partially unfolded III-1 domain, FnIII-1c, induced the expression of a multitude of pro-inflammatory cytokines in human dermal fibroblasts, most notably CXCL1-3, IL-8 and TNF-α. FnIII-1c, a peptide representing an unfolded intermediate structure of the first Type III domain has been shown to initiate the toll-like receptor-4 (TLR4)-NFκB-dependent release of cytokines from human dermal fibroblasts (You, et al., J. Biol. Chem., 2010). Here we demonstrate that FnIII-1c and the alternatively spliced FnEDA domain induce a TLR4 dependent activation of p38 MAP kinase and its downstream effector, MAPKAP Kinase-2 (MK-2), to regulate cytokine expression in fibroblasts. RT-qPCR analysis indicated that the p38-MK-2 pathway regulates IL-8 mRNA stability. Interestingly, addition of FnIII-1c and FnEDA synergistically enhanced TLR4-dependent IL-8 release. These data indicate that Fn contains two Type III domains which can activate TLR signaling to induce an inflammatory response in fibroblasts. Furthermore, our data identifies the NF-κB and p38/MK2 signaling pathways as transducers of signals initiated in response to structural changes in fibronectin.

Remodeling of the fibronectin matrix occurs during a variety of pathological and regenerative processes. Cellular generated tensional forces can alter the secondary and tertiary structure of the fibronectin matrix and regulate the exposure of cryptic activities that directly impact cell behavior. In the present study,

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BackgroundMyopic foveoschisis (MF) is among the leading causes of visual loss in high myopia. However, it remains controversial whether internal limiting membrane (ILM) peeling or gas tamponade is necessary treatment option for MF.MethodsPubMed, EMBASE, CBM, CNKI, WANFANG DATA and VIP databases were systematically reviewed. Outcome indicators were myopic foveoschisis resolution rate, visual acuity improvement and postoperative complications.ResultsNine studies that included 239 eyes were selected. The proportion of resolution of foveoschisis was higher in ILM peeling group than non-ILM peeling group (OR = 2.15, 95% CI: 1.06–4.35; P = 0.03). The proportion of postoperative complications was higher in Tamponade group than non-Tamponade group (OR = 10.81, 95% CI: 1.26–93.02; P = 0.03). However, the proportion of visual acuity improvement (OR = 1.63, 95% CI: 0.56–4.80; P = 0.37) between ILM peeling group and non-ILM peeling group and the proportion of resolution of foveoschisis (OR = 1.80, 95% CI: 0.76–4.28; P = 0.18) between Tamponade group and non-Tamponade group were similar.ConclusionsVitrectomy with internal limiting membrane peeling could contribute to better resolution of myopic foveoschisis than non-peeling, however it does not significantly influence the proportion of visual acuity improvement and postoperative complications. Vitrectomy with gas tamponade is associated with more complications than non-tamponade and does not significantly influence the proportion of visual acuity improvement and resolution of myopic foveoschisis.Electronic supplementary materialThe online version of this article (10.1186/s12886-017-0562-8) contains supplementary material, which is available to authorized users.

Purpose The association between β-peripapillary atrophy and the retinal vasculature in nonpathological high myopia is unclear. The aim of this study is to investigate whether β-peripapillary atrophy contribute to the changes of the retinal vasculature using optical coherence tomography angiography. Methods In a cross-sectional study, one hundred and thirty eyes with nonpathological high myopia were included. β-peripapillary atrophy was analysed using Image J software based on fundus photographs. A 3.0 × 3.0 mm2 grid and a 4.5 × 4.5 mm2 grid were used to scan parafoveal and peripapillary regions using optical coherence tomography angiography, respectively. Vessel density and fractal dimensions of the retina and foveal avascular zone were analysed and quantified using en face projection images. Correlations between the vascular density, foveal avascular zone, and β-peripapillary atrophy were determined. Results Using multivariate analysis, β-peripapillary atrophy was negatively correlated with the vessel density in radial peripapillary capillaries (p=0.002) even after adjusting for other variables. This relationship was also confirmed in the macula (superficial retinal plexus: p < 0.05; deep retinal plexus: p < 0.05). The vessel densities in the nasal and inferior sectors were more strongly correlated with β-peripapillary atrophy. Conclusions There was a negative correlation between β-peripapillary atrophy and the retinal vasculature in highly myopic eyes, especially in radial peripapillary capillaries and deep retinal plexus. β-peripapillary atrophy can be visualized and is a convenient structural feature that can benefit the early diagnosis and detection of chorioretinal atrophy in high myopia.

Anastellin is an angiogenesis inhibitor derived from the first type III repeat of fibronectin (FN). Anastellin binds to fibronectin and promotes the polymerization of soluble fibronectin into a highly polymerized form termed superfibronectin. In addition, anastellin also causes remodeling of pre-existing fibronectin matrix and modulates cell signaling pathways in both endothelial cells and fibroblasts. In the present study, we address the relationship of anastellin’s effects on fibronectin matrix to its effects on p38 MAP kinase (MAPK) activation. Using a mutant form of anastellin which binds to fibronectin matrix, but does not stimulate formation of superfibronectin, we demonstrate that the activation of p38 MAPK by anastellin is not dependent on the formation of superfibronectin. The mutant form of anastellin does stimulate matrix remodeling, but experiments using FN−/− cells show that the effect of anastellin on p38-MAPK activation is completely independent of fibronectin. Anastellin was able to activate p38 MAPK on cells in suspension as well as on cells null for β1 integrins, suggesting that anastellin activity did not require ligation of integrins. These data suggest that the activation of p38 MAPK by anastellin is independent of anastellin’s effects on fibronectin matrix organization.

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