Fig. 6
From: Hypoxia induces calpain activity and degrades SMAD2 to attenuate TGFβ signaling in macrophages
Graphical abstract. TGFβ binds to its receptor (TGFβR1 and TGFβR2), induces phosphorylation of TGFβR1 and downstream signaling molecules like SMAD2. Active SMAD2 translocates to the nucleus to provoke expression of target genes, i.e., TSP1, DST, and MMP2. Hypoxia in combination with TGFβ activates calpain to degrade SMAD2, which in turn attenuates SMAD2-dependent transcriptional activation and thus, diminishes the induction of TSP1, DST, and MMP2