Tissue remodeling following injury involves TGF-β-mediated fibroblast contraction. While these cells are embedded in a fibronectin (FN)-rich matrix, the role of FN-cell interactions in this process is not fully understood. To explore the role of FN matrix presentation, we analyzed the effect of TGF-β on fibroblasts adhered to FN-coated polyacrylamide gel (PAG). Surprisingly, under these conditions TGF-β triggered cell rounding/contraction. This was accompanied by increased Rho activation and MLCK phosphorylation and was reversed by inhibition of Rho kinase. Although fibroblasts are known to bind to fibronectin's RGD and synergy sites, their relative contribution to cell function is not clear. MLC phosphorylation was reduced and cell contraction was reversed when FN's synergy site was blocked, indicating that contraction requires signals from the synergy site in addition to TGF-β mediated Rho activation. Thus, regulating the FN synergy site therapeutically may provide a mechanism for modulating contractile forces during tissue repair.

No abstract

No abstract

stent placement/EndoVAC) (n¼21, 51.2%), stent placement with surgical revision (n¼10, 24.4%), or surgery alone (n¼10, 24.4%). Anastomotic leak did not affect 30-day mortality (7% AL vs 4% no AL, p¼0.2) and the treatment strategy for AL did not influence OS (p¼0.108) or DFS (p¼0.331). After a median follow-up of 35 months, OS and DFS were 101 and 93 months, respectively. On multivariate analysis, diminished OS was associated with AL (p¼0.001), high American Society of Anesthesiologists (ASA) status (p<0.0001), advanced International Union Against Cancer (UICC) stage (p<0.0001), and G3 carcinoma (p¼0.040); reduced DFS with AL (p¼0.037), advanced UICC stage (p<0.0001), G3 carcinoma (p¼0.044), and lymphangiosis carcinomatosa (p¼0.004).

No abstract