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Transforming growth factor‐beta differently regulates urokinase type plasminogen activator and matrix metalloproteinase‐9 expression in mouse macrophages; analysis of intracellular signal transduction
Author(s) -
Mojsilović Sonja S.,
Santibanez Juan F.
Publication year - 2015
Publication title -
cell biology international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.932
H-Index - 77
eISSN - 1095-8355
pISSN - 1065-6995
DOI - 10.1002/cbin.10435
Subject(s) - signal transduction , microbiology and biotechnology , mmp9 , plasminogen activator , transforming growth factor , mapk/erk pathway , transforming growth factor beta , intracellular , smad , chemistry , biology , urokinase receptor , downregulation and upregulation , biochemistry , endocrinology , gene
Transforming growth factor β (TGF‐β) modulates capacity of macrophages to produce urokinase type plasminogen activator (uPA) and matrix metalloproteinase‐9 (MMP9). uPA and MMP9 actively participate in extracellular matrix reorganization and influence macrophages chemotaxis and cell migration. Although, TGF‐β regulates uPA and MMP9 macrophages expression, the underlying intracellular signal mechanisms are not well elucidated so far. Here we have investigated the implication of TGF‐β signaling in the regulation of uPA and MMP9 expression in RAW 264.7 macrophages. The expression of uPA and MMP9 was assessed by zymography, Western blotting and RT‐PCR. The involvement of Smad, MAPK or NFκB signaling pathways was evaluated by using specific inhibitors. Our results indicated that TGF‐β simultaneously increased uPA and reduced MMP9 expression. The Smad3, ERK1,2, and JNK1,2 signaling pathways seem to be the main mechanisms that mediate TGF‐β‐induced uPA expression. Whereas TGF‐β‐reduced MMP9 expression appears to be regulated independently by JNK1,2 activation and by NFκB signaling inhibition. Thus, our results suggested that, in murine macrophages, TGF‐β differentially regulates uPA and MMP9 expressions through different intracellular signaling mechanisms. In addition, presented data may help in understanding the role of TGF‐β in macrophages proteases regulation in inflammatory diseases.