IndraLab
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"Notably, we found that these cellular responses described above did not require persistent TGF-beta1 stimulation (XREF_FIG), indicating that one possible mechanism by which TGF-beta1 triggered down-regulation of ALK5 protein and mRNA expression, leads to the desensitization of the leukocytes toward TGF-beta1 stimulation."
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"Statistical analyses were performed using one-way ANOVA followed by the Fisher least significant difference test for comparisons using SPSS 19.0 software (SPSS, Inc., Chicago, IL, USA), where p < 0.05 was considered significant.ResultsTGF-beta1 upregulated ALK5 and PAI-1 mRNA expression in cultured HTFsEffects of TGF-beta1 treatment on mRNA expression of ALK5 and PAI-1 When HTFs were treated with 10 ng/mL of TGF-beta1 for different lengths of time, mRNA levels of ALK5 changed in a time dependent manner."
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"To assess the link with TGF-β signaling more closely, sEH expression was assessed in macrophages isolated from mice lacking the endogenous Alk5 antagonist, secreted modular calcium-binding protein 1 (SMOC1). xref Indeed, Ephx2 /sEH levels were elevated in M2c macrophages from SMOC1 +/− mice ( xref G and xref H) that lack detectable levels of the SMOC1 protein. xref These results indicated that TGF-β1 activates Alk5 to phosphorylate Smad2 and increases Ephx2 /sEH expression."
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"Further, PAI-1, which is induced by TGF-beta1 activation of the Alk5 and SMAD2/3 pathway, contributes to vessel stabilization by preventing degradation of the provisional matrix deposited around new vessels and favoring the establishment of new basal lamina, again consistently with our finding that PAI-1 was specifically and robustly induced in the low VEGF conditions, leading to the fastest stabilization."