GDF15 mediates renal cell plasticity in response to potassium depletion

Abstract

A low potassium (K+) intake is a common situation in the population of the Westernized countries where processed food is prevalent in the diet. Here, we show that expression of GDF15, a TGFbeta-related growth factor, is increased in renal tubular segments and gut parts of mice in response to low-K+ diet leading to a systemic elevation of its plasma and urine concentration. In human, under mild dietary K+ restriction, we observed that urine GDF15 excretion is correlated with plasma K+ level. Conversely to WT mice, adaptation to K+ restriction of GDF15-KO mice is not optimal, they do not increase their number of type A intercalated cell, responsible for K+ retention, and have a delayed renal K+ retention, leading to early development of hypokalemia. This renal effect of GDF15 depends on ErBb2 receptor, whose expression is increased in the kidney collecting ducts. We also observe that, in the absence of GDF15, the release of K+ by the muscles is blunted which is compensated by a loss of muscle mass. Thus, in this study, we showed that GDF15 plays a central role in the response to K+ restriction by orchestrating the modification of the cell composition of the collecting duct.

Research Progress on the Role and Mechanism of GDF15 in Body Weight Regulation

“…In addition to glucose metabolism and lipid metabolism described in detail below, GDF15 can affect ion metabolism and iron metabolism pathways. GDF15 can mediate proliferative effect on type A intercalated cells through the ErbB2 receptor in the presence of type 2 H,K-ATPase and maintain K+ balance [15]. Hepcidin maintains systemic iron homeostasis, and GDF15 has been shown to regulate iron metabolism by inhibiting hepcidin expression in primary hepatocytes [16].…”

Plasticity

“…In the kidney, for example, Pohl et al 2 have characterized the impressive potential for context-specific remodeling that endothelial cells exhibit. In another example from the same organ system, Lasaad et al 3 have identified a major mediator of renal cell plasticity during the physiological response to reduced K+ uptake.…”

Kidney membrane proteins and epithelial transport

“…Submissions of original articles are also most welcome. In the special series, these have informed on how GDF15 drives renal cell plasticity in response to potassium depletion, 8 and how increased expression of the sodiumdependent phosphate transporter NaPi-2b and paracellular phosphate permeation contribute to determining the high intestinal phosphate absorption in young animals. 9 We cordially invite you to participate in the ongoing special series with either original articles or reviews on the physiology and pathophysiology of epithelial transport.…”