Specific disruption of calcineurin-signaling in the distal convoluted tubule impacts the transcriptome and proteome, and causes hypomagnesemia and metabolic acidosis

Bánki, Eszter; Fisi, Viktoria; Moser, Sandra; Wengi, Agnieszka; Carrel, Monique; Loffing‐Cueni, Dominique; Pentón, David; Kratschmar, Denise V.; Rizzo, Ludovica; Lienkamp, Soeren S.; Odermatt, Alex; Rinschen, Markus M.; Loffing, Johannes

doi:10.1016/j.kint.2021.06.030

Cited by 22 publications

(25 citation statements)

References 57 publications

(80 reference statements)

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“…These large-scale kidney research projects are balancing the application of established multi-omic technologies with continued development of cutting-edge spatially targeted MS approaches. Spatially targeted proteomics utilizing profiling strategies has been more widely applied to the kidney than other technologies, and therefore individual glomerular and tubule proteomes are more well characterized (Betsholtz et al, 2007;Höhne et al, 2018;Hoyer et al, 2019;Späth et al, 2019;Koehler et al, 2020;Sigdel et al, 2020;Banki et al, 2021). Metabolomics has been applied to patient samples and kidney homogenates to great effect, and IMS has broadly characterized the spatial distribution of select small metabolites (Abbiss et al, 2019;Neumann et al, 2020;Zhang et al, 2020).…”

Section: Conclusion and Perspectivementioning

confidence: 99%

Uncovering Molecular Heterogeneity in the Kidney With Spatially Targeted Mass Spectrometry

Kruse

Spraggins

2022

Front. Physiol.

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The kidney functions through the coordination of approximately one million multifunctional nephrons in 3-dimensional space. Molecular understanding of the kidney has relied on transcriptomic, proteomic, and metabolomic analyses of kidney homogenate, but these approaches do not resolve cellular identity and spatial context. Mass spectrometry analysis of isolated cells retains cellular identity but not information regarding its cellular neighborhood and extracellular matrix. Spatially targeted mass spectrometry is uniquely suited to molecularly characterize kidney tissue while retaining in situ cellular context. This review summarizes advances in methodology and technology for spatially targeted mass spectrometry analysis of kidney tissue. Profiling technologies such as laser capture microdissection (LCM) coupled to liquid chromatography tandem mass spectrometry provide deep molecular coverage of specific tissue regions, while imaging technologies such as matrix assisted laser desorption/ionization imaging mass spectrometry (MALDI IMS) molecularly profile regularly spaced tissue regions with greater spatial resolution. These technologies individually have furthered our understanding of heterogeneity in nephron regions such as glomeruli and proximal tubules, and their combination is expected to profoundly expand our knowledge of the kidney in health and disease.

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Section: Conclusion and Perspectivementioning

confidence: 99%

Uncovering Molecular Heterogeneity in the Kidney With Spatially Targeted Mass Spectrometry

Kruse

Spraggins

2022

Front. Physiol.

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“…Also, knockout mouse models have been useful in identifying electrolyte related function of genes that do not encode for transporters (indirect regulation). For example, the roles of Adenylate cyclase 3 ( Adcy3 ) and calcineurin in regulating Mg 2+ handling were described using knockout mouse models 45 , 46 . However, not all knockout mouse models recapitulate the phenotype associated with the human disease.…”

Section: Discussionmentioning

confidence: 99%

FAM111A is dispensable for electrolyte homeostasis in mice

Ilenwabor

Schigt

Kompatscher

et al. 2022

Sci Rep

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Autosomal dominant mutations in FAM111A are causative for Kenny-Caffey syndrome type 2. Patients with Kenny-Caffey syndrome suffer from severe growth retardation, skeletal dysplasia, hypoparathyroidism, hypocalcaemia, hyperphosphataemia and hypomagnesaemia. While recent studies have reported FAM111A to function in antiviral response and DNA replication, its role in regulating electrolyte homeostasis remains unknown. In this study, we assessed the role of FAM111A in the regulation of serum electrolyte balance using a Fam111a knockout (Fam111a−/−) C57BL/6 N mouse model. Fam111a−/− mice displayed normal weight and serum parathyroid hormone (PTH) concentration and exhibited unaltered magnesium, calcium and phosphate levels in serum and 24-hour urine. Expression of calciotropic (including Cabp28k, Trpv5, Klotho and Cyp24a1), magnesiotropic (including Trpm6, Trpm7, Cnnm2 and Cnnm4) and phosphotropic (Slc20a1, Slc20a2, Slc34a1 and Slc34a3) genes in the kidneys, duodenum and colon were not affected by Fam111a depletion. Only Slc34a2 expression was significantly upregulated in the duodenum, but not in the colon. Analysis of femurs showed unaffected bone morphology and density in Fam111a−/− mice. Kidney and parathyroid histology were also normal in Fam111a−/− mice. In conclusion, our study is the first to characterise the function of FAM111A in vivo and we report that mice lacking FAM111A exhibit normal electrolyte homeostasis on a standard diet.

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“…14 Calcium contributed along with other ions like as sodium, potassium and chloride in the disturbance of blood pressure. 15 Essential hypertension can be caused by a change in cellular transportation of ions due to a change in calcium ion concentration. 16,17 Basically vascular tone determines by calcium ions.…”

Section: Discussionmentioning

confidence: 99%

Estimation of Serum Calcium Level in the Patients of Hypertension

Ali¹,

Haque²,

Rauf³

et al. 2022

PJMHS

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Background: Hypertension is one of the leading progressive cause of mortality and morbidity in developed as well as developing countries all over the world. Intracellular and extracellular ions of the body regulate the hemostasis of blood pressure. Objective: To estimate the serum calcium level in the patients of newly diagnosed cases of hypertension with normotensive set of subjects. Methodology: This case comparative study was conducted at the medical OPD of Bilawal Medical College and LUMHS Hospital Hyderabad and Jamshoro. 100 subjects were chosen and divided into two groups: 50 normotensive as a control group and 50 hypertensive as a case study group. Selection of samples was done on the basis of the non-probability technique. A sphygmomanometer was used to measure blood pressure, and a kit method was used to measure serum calcium levels. The statistical analysis of the data was carried out by SPSS version 22 by applying the student t test. Results: The mean age of control group subjects was 44 ± 6 years and control group was 42 ± 7 years. The mean systolic Blood pressure of control group was 110 ± 5 mmHg, while in case study group it was 140 ± 10 mmHg. The mean Diastolic blood pressure of control group was 80 ± 5 mmHg, while in case study group it was 105 ± 5 mmHg. The mean serum calcium level in control group was 9.82 ± 0.68 mg/dl and in case study group it was 8.45 ± 0.47 mg/dl. There was significant (p <0.05) difference of serum calcium level was observed in case study group (hypertensive subjects group). Conclusion: This study concluded that disturbance in intracellular calcium levels can be one of contributory factor in the pathogenesis of essential hypertension. Keywords: Essential Hypertension, Serum Calcium, Intracellular Calcium, Blood Pressure.

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Specific disruption of calcineurin-signaling in the distal convoluted tubule impacts the transcriptome and proteome, and causes hypomagnesemia and metabolic acidosis

Cited by 22 publications

References 57 publications

Uncovering Molecular Heterogeneity in the Kidney With Spatially Targeted Mass Spectrometry

Uncovering Molecular Heterogeneity in the Kidney With Spatially Targeted Mass Spectrometry

FAM111A is dispensable for electrolyte homeostasis in mice

Estimation of Serum Calcium Level in the Patients of Hypertension

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