Epithelial membrane transport and kidney physiology

Abstract

Epithelial membrane transport is fundamental to uphold many physiological processes in the kidney and beyond. Since its founding as Skandinavisches Archiv für Physiologie in 1889, Acta Physiologica has published many groundbreaking studies in this field.^{1, 2} These include August Krogh's discoveries on ion absorption in frog skin and the development of the Ussing chamber system. To honor these and many other contributions, a special series on membrane proteins, epithelial transport, and kidney physiology was launched in Acta Physiologica in 2023.² Now, some two years later, the series is drawing to a close, with only a few manuscripts still under review.

The Acta Physiologica special series has featured both original research articles and full-length reviews, covering recent advances in epithelial transport throughout the various bodily organs, as well as physiological and pathophysiological mechanisms in the kidney. The most recent contributions in this series are highlighted here, and all contributions are now being assembled in a virtual issue.

A central theme of this series is the molecular machinery that drives epithelial transport and its regulation. With respect to the role of tight junctions and paracellular transport, Pouyiourou et al.³ investigated ion permeability profiles of renal paracellular channel-forming claudins. This original study characterized the tight junction proteins in a cell model with minimal endogenous claudin expression.³ Their findings offer key insights into how claudins determine tubular ion permeability along the different segments of the nephron, and thus advance our understanding of selective ion transport in the kidney.⁴

The impact of loop diuretics on renal calcium and magnesium handling is also reviewed. Loop diuretics disrupt the driving force required for paracellular transport in the tubular epithelium, thereby reducing mineral reclamation by the kidney.⁵ In contrast, thiazide diuretics, which are frequently used to reduce blood pressure, limit urinary calcium excretion, and are therefore used to treat kidney stone disease. In this special series, Bargagli et al review the use of thiazides for kidney stone prevention and examine off-target effects on, for example, glucose tolerance.⁶ Another hormone relevant to mineral balance is the anti-aging hormone klotho. For the special series, Grigore et al.⁷ comprehensively review the physiology of klotho-deficient mouse models and provide insights into the role of klotho in the regulation of renal electrolyte transport and mineral balance.

An original study by Lasaad et al.⁸ explores the role of growth differentiation factor 15 (GDF15) in regulating renal collecting duct cell plasticity in response to potassium depletion. Their findings reveal that Gdf15 knockout mice exhibit rapid onset hypokalemia and an inability to increase alpha intercalated cell abundance following dietary potassium restriction. Furthermore, Yuan et al.⁹ review the role of the Piezo-type mechanosensitive ion channel component 1 (Piezo1) in the kidney, highlighting its implications for renal physiology and disease. Finally, the effects of cannabinoids on renal function are reviewed by Didik et al.,¹⁰ examining the expression of the renal cannabinoid receptor systems and how the compound impacts kidney health and disease.

Several interesting manuscripts review how mesangial cells maintain the glomerular filtration barrier as well as the effects of proteinuria on the tubular epithelium. Boi et al.¹¹ focus on the role of the mesangium in glomerular function, offering insights into how these cells contribute to both healthy and diseased kidneys. Furthermore, Faivre et al.¹² review how proteinuria exerts toxic effects on the downstream nephron segments and contribute to the progression of chronic kidney disease.

Epithelial transport extends beyond the kidney. Shimada et al.¹³ provide a detailed review of amino acid flux in the human placenta and relevant animal models. The review explores Systems A and L transport of non-essential and essential amino acids, respectively, highlighting their role in fetal growth. An original article by Nunes et al.¹⁴ investigates how trophoblast-specific knockdown of DEP-domain-containing mTOR-interacting protein (DEPTOR) enhances mTOR signaling, thereby stimulating Systems A and L amino acid transport and fetal growth. In the liver, Van de Graaf et al.¹⁵ review metabolite transport across different liver zones, providing insights into the spatial organization of metabolite transport in hepatic tissue. At the molecular level, Serrano-Novillo et al. investigate the routing of Kv7.1 required for the cardiac slow delayed rectifier potassium currents in association with KCNE1. Their study provides new insights into Kv7.1 channel trafficking to endoplasmic reticulum–plasma membrane junctions.¹⁶

Collectively, these contributions highlight the latest research articles and reviews featured in the special series on membrane proteins, epithelial transport, and kidney physiology.

Henrik Dimke: writing – review and editing; writing – original draft.

The laboratory of Henrik Dimke is supported by grants from the Independent Research Fund Denmark, the Carlsberg Foundation, and the Novo Nordisk Foundation, including a distinguished investigator award.