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Editorial
. 2017 Jan;113(1):6-9.
doi: 10.1093/cvr/cvw236.

Increased canonical WNT/β-catenin signalling and myxomatous valve disease

Sunita Chopra  1 , Nadia Al-Sammarraie  1 , Yimu Lai  1 , Mohamad Azhar  2
Affiliations
Editorial

Increased canonical WNT/β-catenin signalling and myxomatous valve disease

Sunita Chopra et al. Cardiovasc Res. 2017 Jan.
No abstract available

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Figures

Figure 1
Figure 1
Valve development and homeostasis and valve pathogenesis. Elucidation of the WNT/β-catenin mechanisms through which loss of Axin2 affects the developmental transition during valvulogenesis, from cushion formation – cushion remodeling – valve maturation – adult valve homeostasis, will improve basic understanding of the etiology of MVD.
Figure 2
Figure 2
Loss of Axin2 can cause MVD by shifting TGFβ/SMAD3 pathway toward WNT/β-catenin and BMP signaling. This hypothetical model is based on published findings. In the absence of Axin2, TGFβ-dependent SMAD3 signaling is expected to decrease (indicated by a minus [-] sign), whereas both WNT-dependent β-catenin and BMP-dependent SMAD1/5 signaling are likely to increase (indicated a plus [+] sign). Without the WNT, the destruction complex remains in the cytoplasm, where it ubiquitinates β-catenin by β-TrCP. WNT induces the association of the intact complex with phosphorylated LRP. After binding to LRP, the destruction complex still captures and phosphorylates β-catenin, but ubiquitination by β-TrCP is blocked. Newly synthesized β-catenin accumulates. TGFβ2 and/or BMP2 both could bind to TGFβR3, suggesting a crosstalk between TGFβ and BMP pathways. Fibrillin-1 is thought to restrict bioavailability of both TGFβ and BMP ligands. Both endoglin and TGFβR3 facilitates ligand binding to the canonical TGFβ-receptor (TGFβR1/TGFβR2) heteromeric complex. Axin which interacts with SMAD3 and TGFβRs promotes phosphorylation of the TGFβ-specific SMADs (i.e. pSMAD2/3). Canonical BMP signaling occurs through BMP receptors and BMP-specific SMADs (i.e. SMAD1/5). WNT, TGFβ and BMP signaling each induces specific target genes such as Smad7, Axin 2, and Periostin, respectively. Based on the individual activities of WNT, TGFβ, and BMPs in MVD, the overall signaling integration may play an important role in MVD.
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Comment on

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