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. 2023 Oct;239(2):e14046.
doi: 10.1111/apha.14046. Epub 2023 Sep 4.

GDF15 mediates renal cell plasticity in response to potassium depletion in mice

Samia Lasaad  1   2 , Christine Walter  1   2 , Chloé Rafael  1   2 , Luciana Morla  1   2 , Alain Doucet  1   2 , Nicolas Picard  3 , Anne Blanchard  1   2   4 , Yves Fromes  5 , Béatrice Matot  5 , Gilles Crambert  1   2 , Lydie Cheval  1   2
Affiliations

GDF15 mediates renal cell plasticity in response to potassium depletion in mice

Samia Lasaad et al. Acta Physiol (Oxf). 2023 Oct.

Abstract

Objective: To understand the mechanisms involved in the response to a low-K+ diet (LK), we investigated the role of the growth factor GDF15 and the ion pump H,K-ATPase type 2 (HKA2) in this process.

Methods: Male mice of different genotypes (WT, GDF15-KO, and HKA2-KO) were fed an LK diet for different periods of time. We analyzed GDF15 levels, metabolic and physiological parameters, and the cellular composition of collecting ducts.

Results: Mice fed an LK diet showed a 2-4-fold increase in plasma and urine GDF15 levels. Compared to WT mice, GDF15-KO mice rapidly developed hypokalemia due to impaired renal adaptation. This is related to their 1/ inability to increase the number of type A intercalated cells (AIC) and 2/ absence of upregulation of H,K-ATPase type 2 (HKA2), the two processes responsible for K+ retention. Interestingly, we showed that the GDF15-mediated proliferative effect on AIC was dependent on the ErbB2 receptor and required the presence of HKA2. Finally, renal leakage of K+ induced a reduction in muscle mass in GDF15-KO mice fed LK diet.

Conclusions: In this study, we showed that GDF15 and HKA2 are linked and play a central role in the response to K+ restriction by orchestrating the modification of the cellular composition of the collecting duct.

Keywords: ATP12A; ErbB2; cell proliferation; muscle potassium storage; potassium homeostasis.

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References

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