SMAD7

SMAD7

A gene on chromosome 18q21.1 that encodes a SMAD family protein, named for their similarity to the Drosophila gene Mothers Against Decapentaplegic (MAD), which are signal transducers and transcription modulators of multiple signalling pathways. SMAD7 is a nuclear protein that binds the E3 ubiquitin ligase SMURF2. Once bound, the complex translocates to the cytoplasm, where it inhibits TGF(transforming growth factor)-beta and activin signalling by associating with their receptors, preventing SMAD2 access.
 
Molecular pathology
SMAD7 variants have an increased susceptibility to colorectal cancer type 3.
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Smad7 is inactivated through a direct physical interaction with the LIM protein Hic-5/ARA55.
After blocking with 5% non-fat milk, the membranes were transferred to another container and incubated with the primary antibodies of alkaline phosphatase (ALP, ab83259), Runt-related transcription factor 2 (Runx2, ab23981), Osteopontin (OPN, ab8448), E-cadherin (ab40772), N-cadherin (ab18203), Vimentin (ab16700), ZEB1 (ab124512), Snail (ab82846), Osteocalcin (Ocn, ab93876), proliferating cell nuclear antigen (PCNA, ab18197), Cyclin A (ab181591), Cyclin E1 (ab71535), cyclin-dependent kinase 2 (CDK2, ab64669), Cyclin D1 (ab134175), CDK4 (ab199728), Wnt3a (ab28472), Wnt5a (ab229200), Notch 1 (ab52627), Notch 2 (ab8926), Notch 3 (ab23426), p-Smad2 (ab53100), Smad2 (ab33875), Smad4 (ab40759), Smad7 (ab216428), and GAPDH (ab181602) at 4[degrees]C overnight.
For example, SMAD7 rs4939827 was found to be associated with CRC in two GWASs [74, 75].
Builder-M2-like macrophages regulate [beta]-cell proliferation through the release of a variety of trophic factors such as TGF-[beta], which directly induce upregulation of SMAD7 in [beta]-cells.
A phase 2 study showed that reduction of the TGF-[beta] signaling inhibitor SMAD7 by administration of an antisense oligonucleotide (mongersen) resulted in a significant improvement in Crohn's disease (CD) activity compared with placebo [10, 11].
Ponnusamy et al., "Enhancer of zeste homolog 2 inhibition attenuates renal fibrosis by maintaining Smad7 and phosphatase and tensin homolog expression," Journal oftheAmerican Society of Nephrology, vol.
In order to abate excessive TGF-[beta] signaling, the activation of SMAD2/3 is inhibited by SMAD6 and SMAD7 [47, 48].
Arellanes-Robledo et al., "Mechanisms of action of acetaldehyde in the up-regulation of the human [alpha]2(I) collagen gene in hepatic stellate cells: Key roles of Ski, SMAD3, SMAD4, and SMAD7," The American Journal of Pathology, vol.
He et al., "Prolyl oligopeptidase attenuates hepatic stellate cell activation through induction of Smad7 and PPAR-[gamma]," Experimental and Therapeutic Medicine, vol.
Expressions of collagen type I (COL I), collagen type III (COL III), [alpha]-smooth muscle actin (a-SMA), fibronectin (FN), TGF[beta]1, TGF[beta] type I receptor (TGF[beta]RI), TGF[beta] type II receptor (TGF[beta]RII), Smad2, Smad3, phosphorylated Smad2 (pSmad2), phosphorylated Smad3 (pSmad3), Smad4, Smad7, GR, VDR, RXR, and GAPDH (Abcam, Cambridge, MA, USA) in the lung tissues were demonstrated using Western blot analysis and immunochemistry technique according to the manufacturer's instructions as previously described [8].
Brivanlou, "SMAD7 directly converts human embryonic stem cells to telencephalic fate by a default mechanism," Stem Cells, vol.
Komers et al., "miR-21 promotes renal fibrosis in diabetic nephropathy by targeting PTEN and SMAD7," Clinical Science, vol.