Biology subjects

Lasaad, S.

Publications and source records attributed to Lasaad, S..

3 recordsLinked to original sources

bioRxiv2026

Renal adaptation to high salt diet requires tubular Na+ secretion through type A intercalated cells

BackgroundIn the context of increased salt intake in the world population, the understanding of the mechanisms that contribute to its correct renal excretion and therefore, avoid variation of blood volume and blood pressure is of major importance. MethodsMolecular, ex vivo microperfusion on isolated tubules, and integrative analysis, was used to identify, characterize and investigate a Na+ secretion pathway in the collecting duct. ResultsIn collecting duct of mice, salt load induced an increase of the type A intercalated cells (AIC) number, an overexpression of the H(Na),K-ATPase type 2 (HKA2) catalytic subunit Atp12a and a stimulation of the bumetanide-sensitive Na+ secretion in isolated and microperfused tubules. Surprisingly, HKA2KO mice fed a high-salt diet exhibit a strong dysregulation of their Na+ and water balance with a pronounced loss of Na+ and fluid, alkalosis, hypokalemia and low blood pressure. This Bartter-like phenotype is due to an over-inhibition of the thick ascending limb (TAL) related to an elevated PGE2 production. ConclusionOur findings establish that activation of Na+ secretion in AIC act as the fine-tuning knob in the regulation of renal Na+ excretion in response to high salt intake. Its absence is overcompensated by an inhibition of the Na+ transport system of the TAL.

physiology↗

bioRxiv2023

Low exposure to lithium does not induce nephrogenic diabetes insipidus but microcystic dilations of collecting ducts in a long-term rat model

Lithium induces nephrogenic diabetes insipidus (NDI) and microcystic chronic kidney disease (CKD). As clinical studies suggested that NDI is dose-dependent and CKD time-dependent, we investigated the effects of low exposure to lithium in a long-term rat model. Sprague-Dawley rats were randomly fed during six months with normal diet (controls), addition of lithium to diet, or addition of lithium and amiloride to diet, allowing reaching low steady-state plasma lithium concentrations (0.25{+/-}0.06 and 0.43{+/-}0.16 mmol/L, respectively). Exposure to low plasma lithium concentrations did not induce NDI but microcystic dilations of kidney tubules, identified as collecting ducts (CDs) using immunofluorescent staining. Both hypertrophy, characterized by an increase in the ratio of nuclei per tubular area, and microcystic dilations were observed. Principal cell-to-intercalated cell ratio was higher in dilated than in hypertrophied tubules. There was no correlation between aquaporin-2 mRNA levels and cellular remodelling of CDs. Amiloride/lithium co-administration did not allow significant consistent morphometric and cellular composition changes compared to lithium administration. To conclude, rat low exposure to lithium did not induce overt NDI but microcystic dilations of CDs, which include a marked alteration in cell composition of hypertrophied and dilated CDs, suggesting two distinct underlying pathophysiological mechanisms.

pharmacology and toxicology↗

bioRxiv2022

GDF15 mediates renal cell plasticity in response to potassium depletion

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 TGF{beta}-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.

physiology↗