30 research outputs found
Recommended from our members
Cell surfaceâanchored syndecanâ1 ameliorates intestinal inflammation and neutrophil transmigration in ulcerative colitis
Abstract Syndecanâ1 (SDC1), with a variable ectodomain carrying heparan sulphate (HS) chains between different Syndecans, participates in many steps of inflammatory responses. In the process of proteolysis, the HS chains of the complete extracellular domain can be shed from the cell surface, by which they can mediate most of SDC1's function. However, the exact impact on SDC1 which anchored on the cell surface has not been clearly reported. In our study, we established the models by transfection with the cleavable resistant SDC1 mutant plasmid, in which SDC1 shedding can be suppressed during stimulation. Role of membrane SDC1 in inflammatory pathway, proâinflammatory cytokine secretion as well as neutrophil transmigration, and how suppressing its shedding will benefit colitis were further investigated. We found that the patients suffered ulcerative colitis had high serum SDC1 levels,presented with increased levels of P65, tumour necrosis factor alpha (TNFâα) and ILâ1ÎČ and higher circulating neutrophils. NFâÎșB pathway was activated, and secretion of TNFâα, interleukinâ1beta (ILâ1ÎČ), ILâ6 and ILâ8 were increased upon lipopolysaccharide stimuli in intestinal epithelial cells. Syndecanâ1, via its anchored ectodomain, significantly lessened these upâregulation extents. It also functioned in inhibiting transmigration of neutrophils by decreasing CXCLâ1 secretion. Moreover, SDC1 ameliorated colitis activity and improved histological disturbances of colon in mice. Taken together, we conclude that suppression of SDC1 shedding from intestinal epithelial cells relieves severity of intestinal inflammation and neutrophil transmigration by inactivating key inflammatory regulators NFâÎșB, and downâregulating proâinflammatory cytokine expressions. These indicated that compenstion and shedding suppression of cytomembrane SDC1 might be the optional therapy for intestinal inflammation
A cytoskeleton regulator AVIL drives tumorigenesis in glioblastoma
Genes that modulate the cytoskeleton have been associated with increased cell proliferation and migration. Here, the authors show that AVIL, an actin regulatory protein, is overexpressed in glioblastomas and mediates oncogenic effects through regulation of FOXM1 stability and LIN28B expression