ZFIN Image: Metzner et al., 2020, Figure 7

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Figure Caption

Figure 7

Model for role of ALK5 and non-canonical androgen signaling in ADPKD. (a) TGFβ binds to ALK5 (TGFβ-receptor 1) or ALK4 (not shown) at the plasma membrane to activate the transcription factors SMAD2/3. SMAD2/3 in turn activate other TGFβ regulated genes to promote cyst expansion and disease progression by effects on inflammation, extracellular matrix accumulation, proliferation and apoptosis. (b) Androgens bind to androgen receptors (AR) in the cytoplasm resulting in translocation of the complex to the nucleus. The AR-androgen complex modulates gene transcription of androgen related genes in the canonical signaling pathway. Androgens can also bind to and inhibit non-genomic receptors such as L-type calcium channels, ZIP9, GPRC6A or OXER1 in a non-canonical, AR-independent pathway. Androgen activation of this non-canonical pathway promotes cyst expansion and upward tail curvature. Figure created with BioRender.com.

Acknowledgments

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