Matrix metalloproteinase-9 expression is enhanced in renal parietal epithelial cells of zucker XXXX Fatty @entity35 and is induced by @entity21787 in in vitro primary parietal cell culture.

@entity39384 @entity32243 @entity6 @entity2316 @entity10861 @entity3808 @entity6929 @entity21787 @entity35 @entity11017
As a subfamily of matrix metalloproteinases (MMPs), gelatinases including @entity11017 and @entity6929 play an important role in remodeling and homeostasis of the extracellular matrix. However, conflicting results have been reported regarding their expression level and activity in the @entity6 kidney. This study investigated whether and how @entity6929 expression and activity were changed in glomerular epithelial cells upon @entity21787 overload. In situ zymography, immunostaining and Western blot for renal MMP gelatinolytic activity and @entity6929 protein expression were performed in Zucker lean and Zucker @entity6 @entity35 . Confocal microscopy revealed a focal increase in gelatinase activity and @entity6929 protein in the glomeruli of @entity6 @entity35 . Increased glomerular @entity6929 staining was mainly observed in hyperplastic parietal epithelial cells (PECs) expressing @entity32243 in the @entity6 kidneys. Interestingly, increased parietal @entity6929 was often accompanied by decreased staining for podocyte markers (nephrin and @entity39384 ) in the @entity3808 area of affected glomeruli in @entity6 @entity35 . Additionally, urinary excretion of podocyte marker proteins was significantly increased in association with the levels of @entity6929 and @entity21787 in the urine of @entity6 animals. To evaluate the direct effect of @entity21787 on expression and activity of @entity6929 , primary cultured @entity35 glomerular PECs were incubated with rat serum @entity21787 (0.25 - 1 mg/ml) for 24 - 48 hrs. @entity6929 mRNA levels were significantly increased following @entity21787 treatment. Meanwhile, @entity21787 administration resulted in a dose-dependent increase in @entity6929 protein and activity in culture supernatants of PECs. Moreover, @entity21787 activated @entity10861 /42 mitogen-activated protein kinase (MAPK) in PECs. Inhibition of @entity10861 /42 MAPK suppressed @entity21787 -induced @entity6929 secretion from glomerular PECs. Taken together, we have demonstrated that an up-regulation of @entity6929 in activated parietal epithelium is associated with a loss of adjacent podocytes in progressive @entity2316 . @entity21787 overload may induce @entity6929 expression and secretion by PECs via the activation of @entity10861 /42 MAPK pathway.
