Lithium Chloride and GSK3 Inhibition Reduce Aquaporin-2 Expression in Primary Cultured Inner Medullary Collecting Duct Cells Due to Independent Mechanisms

Kaiser, Marc; Edemir, Bayram

doi:10.3390/cells9041060

Cited by 9 publications

(4 citation statements)

References 40 publications

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“…Several studies have shown that the phosphorylation state of AQP2 influences not only the targeting to the apical plasma membrane but also the stability and degradation of the AQP2 42 . We have recently shown that dbcAMP treatment prevents lysosomal degradation of AQP2 34 . Subsequently, we raised the question if the disappearance of AQP3 can be prevented by the activation of PKA signaling.…”

Section: Resultsmentioning

confidence: 99%

“…Membranes were subsequently incubated with primary antibodies in a 1:1.000 dilution. Antibodies raised against AQP2–4 were obtained from Alomone Labs (Jerusalem, Israel) 34 . Antibodies against NHE-1 were obtained from BD Biosciences Pharmingen (San Jose, USA) 35 The reagent Lumilight was added to the membrane for 10 min and the signal was detected with the Lumi Imager F1 (Roche Diagnostics, Basel, Switzerland).…”

Section: Methodsmentioning

confidence: 99%

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Unexpected localization of AQP3 and AQP4 induced by migration of primary cultured IMCD cells

Rose¹,

Kemper²,

Schwab

et al. 2021

Sci Rep

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Aquaporin-2–4 (AQP) are expressed in the principal cells of the renal collecting duct (CD). Beside their role in water transport across membranes, several studies showed that AQPs can influence the migration of cells. It is unknown whether this also applies for renal CD cells. Another fact is that the expression of these AQPs is highly modulated by the external osmolality. Here we analyzed the localization of AQP2–4 in primary cultured renal inner medullary CD (IMCD) cells and how osmolality influences the migration behavior of these cells. The primary IMCD cells showed a collective migration behavior and there were no differences in the migration speed between cells cultivated either at 300 or 600 mosmol/kg. Acute increase from 300 to 600 mosmol/kg led to a marked reduction and vice versa an acute decrease from 600 to 300 mosmol/kg to a marked increase in migration speed. Interestingly, none of the analyzed AQPs were localized at the leading edge. While AQP3 disappeared within the first 2–3 rows of cells, AQP4 was enriched at the rear end. Further analysis indicated that migration induced lysosomal degradation of AQP3. This could be prevented by activation of the protein kinase A, inducing localization of AQP3 and AQP2 at the leading edge and increasing the migration speed.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Unexpected localization of AQP3 and AQP4 induced by migration of primary cultured IMCD cells

Rose¹,

Kemper²,

Schwab

et al. 2021

Sci Rep

Self Cite

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“…Immunofluorescence was performed as described before 64 . Cells were seeded in 24-well plates on glass cover slips.…”

Section: Methodsmentioning

confidence: 99%

The nuclear factor of activated T cells 5 (NFAT5) contributes to the renal corticomedullary differences in gene expression

Chernyakov

Fischer

Brandau

et al. 2022

Sci Rep

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The corticomedullary osmotic gradient between renal cortex and medulla induces a specific spatial gene expression pattern. The factors that controls these differences are not fully addressed. Adaptation to hypertonic environment is mediated by the actions of the nuclear factor of activated T-cells 5 (NFAT5). NFAT5 induces the expression of genes that lead to intracellular accumulation of organic osmolytes. However, a systematical analysis of the NFAT5-dependent gene expression in the kidneys was missing. We used primary cultivated inner medullary collecting duct (IMCD) cells from control and NFAT5 deficient mice as well as renal cortex and inner medulla from principal cell specific NFAT5 deficient mice for gene expression profiling. In primary NFAT5 deficient IMCD cells, hyperosmolality induced changes in gene expression were abolished. The majority of the hyperosmolality induced transcripts in primary IMCD culture were determined to have the greatest expression in the inner medulla. Loss of NFAT5 altered the expression of more than 3000 genes in the renal cortex and more than 5000 genes in the inner medulla. Gene enrichment analysis indicated that loss of NFAT5 is associated with renal inflammation and increased expression of kidney injury marker genes, like lipocalin-2 or kidney injury molecule-1. In conclusion we show that NFAT5 is a master regulator of gene expression in the kidney collecting duct and in vivo loss of NFAT function induces a kidney injury like phenotype.

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“…Proteomics [45] and RNA sequencing [46] demonstrated that several signaling pathways are activated by lithium treatment, such as gene expression, cytoskeletal organization, apoptosis, cell proliferation [45], and an inflammatory-like response [46]. Lithium-induced lysosomal degradation through glycogen synthase kinase-3β (GSK3β) [47] or autophagy-lysosomal degradation through SNX27 might play a role in the downregulation of AQP2 [48]. Lithium was actually considered a potent autophagy inducer, and its autophagy-enhancing property likely contributes to the therapeutic benefit of patients with neuropsychiatric disorders [49].…”

Section: Autophagy-induced Degradation Of Aquaporin 2 In Nephrogenic ...mentioning

confidence: 99%

Autophagy and regulation of aquaporins in the kidneys

Xiang-dong

Kong

Kwon

et al. 2023

Kidney Res Clin Pract

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Aquaporins (AQPs) are water channel proteins that facilitate the transport of water molecules across cell membranes. To date, seven AQPs have been found to be expressed in mammal kidneys. The cellular localization and regulation of the transport properties of AQPs in the kidney have been widely investigated. Autophagy is known as a highly conserved lysosomal pathway, which degrades cytoplasmic components. Through basal autophagy, kidney cells maintain their functions and structure. As a part of the adaptive responses of the kidney, autophagy may be altered in response to stress conditions. Recent studies revealed that autophagic degradation of AQP2 in the kidney collecting ducts leads to impaired urine concentration in animal models with polyuria. Therefore, the modulation of autophagy could be a therapeutic approach to treat water balance disorders. However, as autophagy is either protective or deleterious, it is crucial to establish an optimal condition and therapeutic window where autophagy induction or inhibition could yield beneficial effects. Further studies are needed to understand both the regulation of autophagy and the interaction between AQPs and autophagy in the kidneys in renal diseases, including nephrogenic diabetes insipidus.

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Lithium Chloride and GSK3 Inhibition Reduce Aquaporin-2 Expression in Primary Cultured Inner Medullary Collecting Duct Cells Due to Independent Mechanisms

Cited by 9 publications

References 40 publications

Unexpected localization of AQP3 and AQP4 induced by migration of primary cultured IMCD cells

Unexpected localization of AQP3 and AQP4 induced by migration of primary cultured IMCD cells

The nuclear factor of activated T cells 5 (NFAT5) contributes to the renal corticomedullary differences in gene expression

Autophagy and regulation of aquaporins in the kidneys

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