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Porcupine's dilemma in kidney fibrosis
1Division of Nephrology and Endocrinology, The University of Tokyo Graduate School of Medicine, Tokyo, Japan.
Abstract:
Aberrant activation of Wnt/β-catenin signaling, an activity that is critically modulated by porcupine, a membrane-bound O-acyltransferase, is profibrotic. Previously, the Crowley laboratory demonstrated that oral administration of porcupine inhibitor attenuated experimental mouse kidney fibrosis. Now Lu et al., from that laboratory, using conditional knockout lineages, have shown that porcupine in the renal tubule accelerated fibrosis and Wnt generation, whereas myeloid cell porcupine counteracted the effect. Thus, porcupine has been attracting both positive and negative attention.
Insights
Porcupine inhibition can treat kidney fibrosis. In this study, porcupine in kidney tubules worsened fibrosis, but in myeloid cells, it had a protective effect, highlighting its complex role in Wnt/β-catenin signaling.
Area of Science:
- Nephrology
- Molecular Biology
- Cell Biology
Background:
- Aberrant Wnt/β-catenin signaling promotes kidney fibrosis.
- Porcupine (a membrane-bound O-acyltransferase) is a key regulator of Wnt/β-catenin signaling.
- Previous studies showed porcupine inhibitors can attenuate kidney fibrosis.
Purpose of the Study:
- To investigate the specific roles of porcupine in different kidney cell types regarding fibrosis.
- To understand the dual effects of porcupine in renal tubule and myeloid cells.
Main Methods:
- Utilized conditional knockout mouse models to delete porcupine in specific cell lineages.
- Analyzed the impact of porcupine deletion on kidney fibrosis progression.
- Assessed Wnt signaling activation in response to porcupine modulation.
Main Results:
- Porcupine expression in renal tubules accelerated kidney fibrosis and Wnt generation.
- Porcupine expression in myeloid cells counteracted pro-fibrotic effects.
- These findings reveal cell-specific functions of porcupine in kidney fibrosis.
Conclusions:
- Porcupine's role in kidney fibrosis is complex and cell-dependent.
- Targeting porcupine in specific cell types may offer a refined therapeutic strategy for kidney fibrosis.
- Further research is warranted to explore the therapeutic potential of modulating porcupine in distinct cellular contexts.
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