Figure - PMC

Skip to main content

An official website of the United States government

Here's how you know

Here's how you know

Official websites use .gov
A .gov website belongs to an official government organization in the United States.

Secure .gov websites use HTTPS
A lock ( ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.

View full-text article in PMC

. 2019 May 3;7:176. doi: 10.3389/fped.2019.00176

Search in PMC
Search in PubMed
View in NLM Catalog
Add to search

Copyright © 2019 Lecarpentier, Gourrier, Gobert and Vallée.

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

PMC Copyright notice

Influence of TGF-β1 on the balance between the canonical WNT/β-catenin signaling and PPARγ. In the presence of the WNT ligands, the WNT receptor binds both LRP5/6 and FZD receptors to initiate LRP phosphorylation and DSH-mediated Frizzled internalization. This leads to the dissociation of the GSK-3 β/AXIN/APC destruction complex. Phosphorylation of β-catenin is inhibited and β-catenin accumulates in the cytosol and then translocates to the nucleus to bind TCF-LEF transcription factors. This leads to the WNT-response gene transcription (PDK, MCT-1, cMyc, and Cyclin D1). PPARγ inhibits the β-catenin/TCF-LEF-induced activation of WNT target genes. TGF-β also enhances WNT signaling through the inhibition of DKK1. DKK1 is activated by PPARγ. TGF-β1 binds type 2 TGF-βR2 receptor (TGF-βR2), which recruits type 1 TGF-βR1 receptor (TGF-βR1). This results in the formation of a heterotetramer that phosphorylates Smad. The Smad complex then translocates to the nucleus and regulates the transcription of target genes (CTGF, COL1A). A non-Smad pathway also occurs through PI3K-AKT. PTEN inhibits PI3K-AKT and PPARγ inhibits AKT. APC, adenomatous polyposis coli; CTGF, Connective tissue growth factor; DKK1, Dickkopf-1; DSH, Disheveled; FZD, Frizzled; GSK-3β, glycogen synthase kinase-3β; LRP5/6, low-density lipoprotein receptor-related protein 5/6; MCT-1, monocarboxylate lactate transporter-1; PPARγ, peroxisome proliferator-activated receptor gamma; PI3K, phosphatidylinositol 3-kinase and AKT, AKT/Protein Kinase B; PTEN, Phosphatase and tensin homolog; PDK, pyruvate; dehydrogenase kinase; TCF/LEF, T-cell factor/lymphoid enhancer factor; TGF, Transforming Growth Factor.