Snail homolog 1 is involved in epithelial-mesenchymal transition-like processes in human glioblastoma cells.

Despite advancements in neurosurgery, chemotherapy and radiation therapy, the outcome of patients with glioblastoma remains poor. The migration of tumor cells from the primary tumor site with subsequent invasion of these cells into the surrounding normal brain tissue is frequently responsible for relapse and treatment failure. The present study hypothesized that snail homolog 1 (SNAI1), a factor critically involved in the epithelial-mesenchymal transition (EMT) of human carcinoma cells, may also contribute to an invasive EMT-like phenotype of glioblastoma cells. The majority of glioblastoma cell lines investigated in the present study expressed SNAI1 at basal levels. The present study overexpressed SNAI1 in glioblastoma cell lines by lentiviral transfer of human SNAI1 complementary DNA. In addition, the inhibition of SNAI1 expression was achieved by lentiviral transfer of a short hairpin RNA specific for SNAI1. SNAI1 overexpression increased proliferation of one of the cell lines, U251MG, but exhibited only a weak effect on the migration and invasion of glioblastoma cells. However, downregulation of SNAI1 significantly decreased the invasive capacity of all investigated cell lines. In parallel, regained expression of E-cadherin, a marker that is usually lost during EMT, was observed subsequent to SNAI1 knockdown in the glioblastoma cell lines U87MG and U251MG. The data of the present study suggest that certain key genes of the EMT in carcinoma are also involved in the migration and invasion of human glioblastoma cells.

Circulating fibronectin contributes to mesangial expansion in a murine model of type 1 diabetes.

Fibronectin is ubiquitously expressed in the extracellular matrix, and its accumulation in the glomerular mesangium in diabetic nephropathy is associated with deterioration of renal function in these patients. However, the exact role of fibronectin in the pathogenesis of diabetic nephropathy remains unknown. To clarify this, we administered fluorescent-labeled plasma fibronectin to wild-type mice and found it to accumulate in the mesangium. Using liver-specific conditional-knockout mice to decrease circulating fibronectin, we reduced circulating fibronectin by more than 90%. In streptozotocin-induced diabetes of these knockout mice, the pronounced fall in circulating fibronectin resulted in a decrease in mesangial expansion by 25% and a decline in albuminuria by 30% compared to diabetic control mice. Indeed, the amount of fibronectin in the kidney was reduced, as was the total amount of collagen. In vitro experiments confirmed that matrix accumulation of fibronectin was enhanced by increasing fibronectin only, glucose only, or the combination of both. Thus, circulating fibronectin contributes to mesangial expansion and exacerbation of albuminuria in a murine model of type 1 diabetes.