fig4

Role of inflammation in the progression of diabetic kidney disease

Figure 4. Wnt and TGF-β signaling pathways. To the left of the figure, Wnt canonical and non-canonical pathways are demonstrated. The top left of the sphere features the canonical Wnt/β-Catenin pathway with no ligand bound, leading to the formation of the β-Catenin destruction complex. The top right of the sphere shows the canonical Wnt/β-Catenin pathway when a ligand is bound, allowing target genes to be transcribed, many of which promote fibrosis and EMT. This is achieved by accumulating β-Catenin through the inhibition of the destruction complex. The bottom right showcases the TGF-β pathway which moves through SMAD proteins and interacts closely with both the Wnt/β-Catenin pathway and other traditional inflammatory pathways. Lastly, the bottom left of the sphere shows what is occurring in the Wnt non-canonical pathways when the pro-inflammatory Wnt5a ligand is bound. Non-canonical signaling involves the Ca+ pathway and the PCP (Planar Cell Polarity) pathways. The non-canonical pathways are much more complex than canonical signaling and involve interactions with other pathways through players such as NFAT, PKC, and JNK. This can also lead to inhibition of β-Catenin accumulation. To the right of the figure, phosphorylation interactions between JNK with β-Catenin, specifically at Ser-37 and Thr-41, leads to the destabilization of junctions in the context of cellular adhesion and motility. This is due to the loss of α-Catenin when JNK is bound to the respective residues. AP-1: Activator protein 1; APC: adenomatous polyposis coli; CD146: cluster of differentiation 146; Cdc42: cell division control protein 42; CKIα: casein kinase I alpha; GSK-3β: glycogen synthase kinase 3 beta; JNK: c-Jun N-terminal kinase; LEF: lymphoid enhancer-binding factor; NFAT: nuclear factor of activated T cells; PKC: protein kinase C; Rac1: Ras-related C3 botulinum toxin substrate 1; ROR2: receptor tyrosine kinase-like orphan receptor 2; SARA: SMAD anchor for receptor activation; TCF: T-cell factor; TGF-β: transforming growth factor-β.

Vessel Plus
ISSN 2574-1209 (Online)
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