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. Author manuscript; available in PMC: 2018 Mar 1.
Published in final edited form as: Radiat Res. 2017 Feb 22;187(3):367–381. doi: 10.1667/RR14623.1

Fig. 9.

Fig. 9

Graphical summary of the results. Radiation activates latent TGF-β1 by detaching it from the latency-associated protein (LAP). Activated TGF-β1 binds to TGF-βR2. TGF-βR1 then binds to TGF-βR2. Heterodimerized TGF-β receptors then phosphorylate SMAD2 and SMAD3 in the cytosol. Phosphorylated SMADs then localize to the nucleus after dimerizing with SMAD4. pSMAD2-SMAD4 and pSMAD3-SMAD4 then bind to the promoter region of their target genes and initiate profibrotic and senescence-inducing gene expression. Inhibition of NOX4 inhibits expression of extracellular TGF-b1 and total SMAD3 as well as phosphorylation of SMAD2. MnTE-2-PyP (T2E) inhibits expression of TGF-βR2, SMAD2, SMAD3, SMAD4 and the phosphorylation of SMAD2. As a result, in both of the conditions, inhibition of NOX4 and T2E treatment, profibrotic- and senescence-inducing gene expression is inhibited. As a consequence, inhibition of NOX4 or MnTE-2-PyP-treated irradiated cells become protected from radiation-induced fibrosis and senescence.