1. Figure 4 Potential therapeutic strategies to inhibit TGF-β1/Smad-induced tissue fibrosis
Figure 4 | Potential therapeutic strategies to inhibit TGF-β1/Smad-induced tissue fibrosis. Soluble active TGF-β1 can be inhibited from binding to the TGF-β receptor 2 (TGFR2) receptor through the use of neutralizing antibodies, soluble receptors or the naturally occurring binding molecule decorin (1). The kinase activity of the activated TGFR1 can be inhibited by selective kinase inhibitors to prevent phosphorylation of Smad2/3 (2). Small molecules, such as the Smad3 inhibitor, SIS3, can prevent Smad3 phosphorylation and Smad complex formation (3). Gene transfer-based overexpression of Smad7 can compete with Smad2 and Smad3 for binding to activated TGFR1 (4). Histone deacetylase (HDAC) inhibitors can interfere with epigenetic modifications to reduce the transcription of profibrotic molecules (5). Locked nucleic acid (LNA) anti-sense miRNA can be used to downregulate profibrotic microRNA (miRNA) and long noncoding RNA (lncRNA), whereas antifibrotic miRNA can also be overexpressed (6). α-SMA, α-smooth muscle actin; TIMP, tissue inhibitor of matrix metalloproteinases.
Meng, X.-m. et al. (2016) TGF-β: the master regulator of fibrosis
Nat. Rev. Nephrol. doi: /nrneph