bims-bicyki 2022-10-16 papers

bims-bicyki

Biomed News

on Bicaudal-C1 and interactors in cystic kidney disease

Issue of 2022–10–16
nine papers selected by
Céline Gagnieux, École Polytechnique Fédérale de Lausanne

Acceptance of Illness, Satisfaction with Life, and Emotional Control in the Early Stage of Autosomal Dominant Polycystic Kidney Disease.
Fluorescence imaging of beta cell primary cilia.
Recurrent urinary tract infections in kidney transplant patients with polycystic kidneys.
Shedding of ciliary vesicles at a glance.
Differentiated dynamic response in C. elegans chemosensory cilia.
Author Correction: A high-throughput screening platform for Polycystic Kidney Disease (PKD) drug repurposing utilizing murine and human ADPKD cells.
Histopathological Features of Pendred Syndrome Thyroids Align with Differences in the Expression of Thyroid-Specific Markers, Apical Iodide Transporters, and Ciliogenesis Process.
NEK8-Associated Nephropathies: Do Autosomal Dominant Forms Exist?
The centrosomal protein 83 (CEP83) regulates human pluripotent stem cell differentiation towards the kidney lineage.

Nephron. 2022 Oct 12. 1-6

Acceptance of Illness, Satisfaction with Life, and Emotional Control in the Early Stage of Autosomal Dominant Polycystic Kidney Disease.

Magdalena Jankowska, Anna Walerzak, Michał Harciarek, Bolesław Rutkowski, Alicja Dębska-Ślizień.

   INTRODUCTION: Psychological disorders are strong predictors of life expectancy and have an impact on quality of life. Autosomal dominant polycystic kidney disease (ADPKD) is frequently diagnosed before the onset of subjective symptoms. Similar to other disorders of genetic origin, ADPKD may be a source of remarkable psychological discomfort. One way of coping with emotional distress is its suppression, and this could be measured. Our study aimed to provide data on the acceptance of illness, the emotional suppression of anger, and both anxiety and depression as well as satisfaction with life in young patient population of early-stage ADPKD in comparison to healthy demographically matched individuals.
METHODS: Fifty patients in the asymptomatic stage of ADPKD with an eGFR >60 mL/min (4p MDRD) and 50 healthy demographically matched individuals were included in this study. Participants filled out a set of psychological questionnaires: Acceptance of Illness Scale (AIS), Courtauld Emotional Control Scale (CECS), and Satisfaction with Life Scale (SWLS).
RESULTS: Asymptomatic patients with ADPKD had 80% scores indicative of disease acceptance in AIS. As compared to healthy individuals, they presented with significantly stronger suppression of both anxiety and depression but not anger. The ADPKD group had significantly lower satisfaction with life in comparison to the healthy group.
CONCLUSION: Asymptomatic ADPKD patients had a high level of disease acceptance. Anger suppression in this group was comparable to healthy individuals, but anxiety and depression were controlled more intensively. Despite the asymptomatic course of the disease, ADPKD patients revealed lower satisfaction with life in comparison to healthy persons.

Keywords:  Anger; Anxiety; Autosomal dominant polycystic kidney disease; Depression; Psychonephrology

DOI:  https://doi.org/10.1159/000526840
Front Endocrinol (Lausanne). 2022 ;13 1004136

Fluorescence imaging of beta cell primary cilia.

Zipeng A Li, Jung Hoon Cho, Louis G Woodhams, Jing W Hughes.

  Primary cilia are slender cell-surface organelles that project into the intercellular space. In pancreatic beta cells, primary cilia coordinate a variety of cell responses including GPCR signaling, calcium influx, and insulin secretion, along with likely many underappreciated roles in islet development and differentiation. To study cilia function in islet biology, direct visualization of primary cilia by microscopic methods is often a necessary first step. Ciliary abundance, distribution, and morphology are heterogeneous among islet cells and are best visualized by fluorescence microscopy, the tools for which are readily accessible to most researchers. Here we present a collection of fluorescence imaging methods that we have adopted and optimized for the observation of primary cilia in mouse and human islets. These include conventional confocal microscopy using fixed islets and pancreas sections, live-cell imaging with cilia-targeted biosensors and probes, cilia motion recordings, and quantitative analysis of primary cilia waveform in the ex vivo environment. We discuss practical considerations and limitations of our approaches as well as new tools on the horizon to facilitate the observation of primary cilia in pancreatic islets.

Keywords:  Cilia; beta cell (β-cell); fluorescence; live-cell; microscopy

DOI:  https://doi.org/10.3389/fendo.2022.1004136
Vnitr Lek. 2022 ;68(E-4): 4-9

Recurrent urinary tract infections in kidney transplant patients with polycystic kidneys.

Marcel Čellár, Martina Konko Ová, Eva Lacková, Terézia Hrubá, Peter Galajda, Ivana Dedinská.

INTRODUCTION: Kidney transplantation is now a routine method used to treat end-stage renal disease. About 10 % of kidney transplant patients are patients with autosomal dominant polycystic kidney disease (ADPKD). After successful kidney transplantation, recurrent urinary tract infections also occur in initially asymptomatic patients.
MATERIAL AND METHODS: The group included 320 patients after kidney transplantation. We compared patients with ADPKD versus patients without ADPKD in terms of the presence of recurrent urinary tract infections.
THE RESULTS: The incidence of recurrent urinary tract infections (rIMCs) was 18% in patients without ADPKD and 48% in patients without ADPKD. Nephrectomy after kidney transplantation due to recurrent urinary tract infections eliminated this infectious complication (in 86% of patients).
CONCLUSION: Kidney transplant patients with ADPKD have a significantly higher incidence of recurrent urinary tract infections. Removal of polycystic kidneys is a suitable solution if the infection persists.

Keywords: ADPKD; Transplantation; kidneys; polycystic kidneys; recurrent urinary tract infection
J Cell Sci. 2022 Oct 01. pii: jcs246553. [Epub ahead of print]135(19):

Shedding of ciliary vesicles at a glance.

Irene Ojeda Naharros, Maxence V Nachury.

  Cilia sense and transduce sensory stimuli, homeostatic cues and developmental signals by orchestrating signaling reactions. Extracellular vesicles (EVs) that bud from the ciliary membrane have well-studied roles in the disposal of excess ciliary material, most dramatically exemplified by the shedding of micrometer-sized blocks by photoreceptors. Shedding of EVs by cilia also affords cells with a powerful means to shorten cilia. Finally, cilium-derived EVs may enable cell-cell communication in a variety of organisms, ranging from single-cell parasites and algae to nematodes and vertebrates. Mechanistic understanding of EV shedding by cilia is an active area of study, and future progress may open the door to testing the function of ciliary EV shedding in physiological contexts. In this Cell Science at a Glance and the accompanying poster, we discuss the molecular mechanisms that drive the shedding of ciliary material into the extracellular space, the consequences of shedding for the donor cell and the possible roles that ciliary EVs may have in cell non-autonomous contexts.

Keywords:  Autotomy; Cilia; Decapitation; Ectocytosis; Ectosomes; Extracellular vesicles; Shedding

DOI:  https://doi.org/10.1242/jcs.246553
Cell Rep. 2022 Oct 11. pii: S2211-1247(22)01321-3. [Epub ahead of print]41(2): 111471

Differentiated dynamic response in C. elegans chemosensory cilia.

Christine W Bruggeman, Guus H Haasnoot, Noémie Danné, Jaap van Krugten, Erwin J G Peterman.

  Cilia are membrane-enveloped organelles that protrude from the surface of most eurokaryotic cells and play crucial roles in sensing the external environment. For maintenance and function, cilia are dependent on intraflagellar transport (IFT). Here, we use a combination of microfluidics and fluorescence microscopy to study the response of phasmid chemosensory neurons, in live Caenorhabditis elegans, to chemical stimuli. We find that chemical stimulation results in unexpected changes in IFT and ciliary structure. Notably, stimulation with hyperosmotic solutions or chemical repellents results in different responses, not only in IFT, ciliary structure, and cargo distribution, but also in neuronal activity. The response to chemical repellents results in habituation of the neuronal activity, suggesting that IFT plays a role in regulating the chemosensory response. Our findings show that cilia are able to sense and respond to different external cues in distinct ways, highlighting the flexible nature of cilia as sensing hubs.

Keywords:  CP: Cell biology; Caenorhabditis elegans; chemosensation; chemosensory phasmid neurons; intraflagellar transport; microfluidics; neuronal signaling

DOI:  https://doi.org/10.1016/j.celrep.2022.111471
Sci Rep. 2022 Oct 13. 12(1): 17185

Author Correction: A high-throughput screening platform for Polycystic Kidney Disease (PKD) drug repurposing utilizing murine and human ADPKD cells.

Rosita R Asawa, Carina Danchik, Alexey Zakharov, Yuchi Chen, Ty Voss, Ajit Jadhav, Darren P Wallace, Josephine F Trott, Robert H Weiss, Anton Simeonov, Natalia J Martinez.

DOI: https://doi.org/10.1038/s41598-022-21947-1
Endocr Pathol. 2022 Oct 15.

Histopathological Features of Pendred Syndrome Thyroids Align with Differences in the Expression of Thyroid-Specific Markers, Apical Iodide Transporters, and Ciliogenesis Process.

V Vázquez-Román, J M Cameselle-Teijeiro, J M Fernández-Santos, M J Ríos-Moreno, L Loidi, T Ortiz, I Martín-Lacave.

  Pendred syndrome (PDS) is an autosomal recessive disorder caused by mutations in the gene that encodes pendrin. Pendred thyroid tissue is supposedly altered by the absence of functional pendrin, but it is still unknown whether other iodide exchangers could compensate for the loss of the protein. Moreover, we have recently described that primary cilium, a conserved structure present at the apical surface of normal follicular cells, suffers different alterations in functional thyroid diseases. We aimed (1) to better understand the histopathological changes experienced by PDS thyroids, (2) to analyze the expression of different thyroid-specific genes and alternative iodide transporters and, finally, (3) to determine whether those changes may alter the morphological pattern of primary cilia in follicular cells. Thyroid samples from a series of four PDS patients were analyzed by immunohistochemistry, double immunofluorescence, and morphometry to evaluate changes in primary cilia frequency and length. We found thyroid follicular nodular disease in all PDS thyroids, frequently in association with follicular adenomas. There were only slight changes in the expression of thyroid-specific markers. Although no positivity for pendrin was found, cytoplasmic immunostaining for ANO-1, CLC-5, and CFTR was stronger in diffuse hyperplastic areas when compared to areas with highly cellular follicular nodules (HCFNs). HCFNs and follicular adenomas always showed diminished ciliary frequency and length. Our results suggest a direct relationship between the absence of functional pendrin and the loss of the normal thyroid architecture in PDS patients, which was also accompanied by differences in the expression of specific immunohistochemical markers and altered ciliogenesis. The present data may help the pathologist in screening for PDS.

Keywords:  Ciliogenesis; Follicular cells; Immunohistochemistry; Iodide channels; Pendred syndrome; Primary cilia

DOI:  https://doi.org/10.1007/s12022-022-09732-2
Nephron. 2022 Oct 10. 1-5

NEK8-Associated Nephropathies: Do Autosomal Dominant Forms Exist?

Cybel Mehawej, Eliane Chouery, Ramy Ghabril, Sima Tokajian, Andre Megarbane.

   INTRODUCTION: Nephronophthisis (NPHP) is a group of autosomal recessive renal diseases characterized by a reduced ability of the kidneys to concentrate solutes, chronic tubulointerstitial nephritis, and cystic kidney disease. It represents the most common genetic cause of childhood renal failure. To date, around 20 different genes, encoding primary cilia proteins, have been linked to NPHP. These contribute to one-third of cases with NPHP while the majority of patients remain molecularly undiagnosed.
MATERIALS AND METHODS: Whole exome sequencing (WES) was carried out on a 2-year-old Lebanese boy with infantile NPHP characterized by multicystic kidney dysplasia, kidney insufficiency, and enlarged kidneys in addition to chronic anemia. The candidate variant, detected by WES, was then tested in the patient and his parents by Sanger sequencing. Copy number variation (CNV) analysis was subsequently performed in the proband.
RESULTS: Our studies enabled the detection of a heterozygous de novo variant in NEK8 (NM_178170: p.Arg45Trp) in the proband. CNV analysis excluded the presence of big deletions or insertions in this gene.
CONCLUSION: Here we report a de novo heterozygous variant in the NEK8 gene in infantile NPHP. This variant was previously detected at a de novo state in a patient presenting with the same clinical features as the proband. This suggests that autosomal dominant forms of NEK8-linked nephropathies may exist. Reporting further patients with NEK8 mutations is essential to confirm these findings and assess whether dominant forms of the disease are restricted to a specific mutational spot or are linked to variants scattered throughout the NEK8 gene.

Keywords:  Autosomal dominant; Genetic variant; NEK8; Nephronophthisis

DOI:  https://doi.org/10.1159/000526841
Elife. 2022 Oct 12. pii: e80165. [Epub ahead of print]11

The centrosomal protein 83 (CEP83) regulates human pluripotent stem cell differentiation towards the kidney lineage.

Fatma Mansour, Christian Hinze, Narasimha Swamy Telugu, Jelena Kresoja, Iman B Shaheed, Christian Mosimann, Sebastian Diecke, Kai M Schmidt-Ott.

  During embryonic development, the mesoderm undergoes patterning into diverse lineages including axial, paraxial, and lateral plate mesoderm (LPM). Within the LPM, the so-called intermediate mesoderm (IM) forms kidney and urogenital tract progenitor cells, while the remaining LPM forms cardiovascular, hematopoietic, mesothelial, and additional progenitor cells. The signals that regulate these early lineage decisions are incompletely understood. Here, we found that the centrosomal protein 83 (CEP83), a centriolar component necessary for primary cilia formation and mutated in pediatric kidney disease, influences the differentiation of human induced pluripotent stem cells (hiPSCs) towards intermediate mesoderm. We induced inactivating deletions of CEP83 in hiPSCs and applied a 7 day in vitro protocol of intermediate mesoderm kidney progenitor differentiation, based on timed application of WNT and FGF agonists. We characterized induced mesodermal cell populations using single cell and bulk transcriptomics and tested their ability to form kidney structures in subsequent organoid culture. While hiPSCs with homozygous CEP83 inactivation were normal regarding morphology and transcriptome, their induced differentiation into IM progenitor cells was perturbed. Mesodermal cells induced after 7 days of monolayer culture of CEP83-deficient hiPCS exhibited absent or elongated primary cilia, displayed decreased expression of critical IM genes (PAX8, EYA1, HOXB7), and an aberrant induction of LPM markers (e. g. FOXF1, FOXF2, FENDRR, HAND1, HAND2). Upon subsequent organoid culture, wildtype cells differentiated to form kidney tubules and glomerular-like structures, whereas CEP83-deficient cells failed to generate kidney cell types, instead upregulating cardiomyocyte, vascular, and more general LPM progenitor markers. Our data suggest that CEP83 regulates the balance of intermediate mesoderm and lateral plate mesoderm formation from human pluripotent stem cells, identifying a potential link between centriolar or ciliary function and mesodermal lineage induction.

Keywords:  cell biology; developmental biology; human

DOI:  https://doi.org/10.7554/eLife.80165