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Article ; Online: TRPC Channels in the Physiology and Pathophysiology of the Renal Tubular System

Colya N. Englisch / Friedrich Paulsen / Thomas Tschernig

International Journal of Molecular Sciences, Vol 24, Iss 1, p

What Do We Know?

2022 Volume 181

Abstract: The study of transient receptor potential (TRP) channels has dramatically increased during the past few years. TRP channels function as sensors and effectors in the cellular adaptation to environmental changes. Here, we review literature investigating ... ...

Abstract	The study of transient receptor potential (TRP) channels has dramatically increased during the past few years. TRP channels function as sensors and effectors in the cellular adaptation to environmental changes. Here, we review literature investigating the physiological and pathophysiological roles of TRPC channels in the renal tubular system with a focus on TRPC3 and TRPC6. TRPC3 plays a key role in Ca 2+ homeostasis and is involved in transcellular Ca 2+ reabsorption in the proximal tubule and the collecting duct. TRPC3 also conveys the osmosensitivity of principal cells of the collecting duct and is implicated in vasopressin-induced membrane translocation of AQP-2. Autosomal dominant polycystic kidney disease (ADPKD) can often be attributed to mutations of the PKD2 gene. TRPC3 is supposed to have a detrimental role in ADPKD-like conditions. The tubule-specific physiological functions of TRPC6 have not yet been entirely elucidated. Its pathophysiological role in ischemia-reperfusion injuries is a subject of debate. However, TRPC6 seems to be involved in tumorigenesis of renal cell carcinoma. In summary, TRPC channels are relevant in multiples conditions of the renal tubular system. There is a need to further elucidate their pathophysiology to better understand certain renal disorders and ultimately create new therapeutic targets to improve patient care.
Keywords	TRPC3 ; TRPC6 ; kidney ; renal tubular system ; transient receptor potential ; renal carcinoma ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Subject code	616
Language	English
Publishing date	2022-12-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Immunohistochemistry Reveals TRPC Channels in the Human Hearing Organ—A Novel CT-Guided Approach to the Cochlea

Colya N. Englisch / Jakob Steinhäuser / Silke Wemmert / Martin Jung / Joshua Gawlitza / Gentiana Wenzel / Bernhard Schick / Thomas Tschernig

International Journal of Molecular Sciences, Vol 24, Iss 9290, p

2023 Volume 9290

Abstract: TRPC channels are critical players in cochlear hair cells and sensory neurons, as demonstrated in animal experiments. However, evidence for TRPC expression in the human cochlea is still lacking. This reflects the logistic and practical difficulties in ... ...

Abstract	TRPC channels are critical players in cochlear hair cells and sensory neurons, as demonstrated in animal experiments. However, evidence for TRPC expression in the human cochlea is still lacking. This reflects the logistic and practical difficulties in obtaining human cochleae. The purpose of this study was to detect TRPC6, TRPC5 and TRPC3 in the human cochlea. Temporal bone pairs were excised from ten body donors, and the inner ear was first assessed based on computed tomography scans. Decalcification was then performed using 20% EDTA solutions. Immunohistochemistry with knockout-tested antibodies followed. The organ of Corti, the stria vascularis, the spiral lamina, spiral ganglion neurons and cochlear nerves were specifically stained. This unique report of TRPC channels in the human cochlea supports the hypothesis of the potentially critical role of TRPC channels in human cochlear health and disease which has been suggested in previous rodent experiments.
Keywords	TRPC6 ; TRPC5 ; TRPC3 ; human cochlea ; organ of Corti ; temporal bone ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Language	English
Publishing date	2023-05-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: TRPC6 Is Found in Distinct Compartments of the Human Kidney

Colya N. Englisch / Daniel Röhricht / Mariesa Walz / Kerstin Junker / Anja Beckmann / Carola Meier / Friedrich Paulsen / Martin Jung / Thomas Tschernig

International Journal of Translational Medicine, Vol 2, Iss 13, Pp 156-

2022 Volume 163

Abstract: In the context of renal proteinuric diseases, TRPC6 has been shown to play an important role in ultrafiltration associated with the slit diaphragm through the control of the intracellular Ca 2+ concentration in the podocytes of glomeruli. However, to ... ...

Abstract	In the context of renal proteinuric diseases, TRPC6 has been shown to play an important role in ultrafiltration associated with the slit diaphragm through the control of the intracellular Ca 2+ concentration in the podocytes of glomeruli. However, to date, the properties of TRPC6 have been studied mainly in cell lines or in animal models. Therefore, the aim of the study presented here was to investigate the presence and distribution of TRPC6 in human kidneys in order to possibly verify the applicability of the results previously obtained in nonhuman experiments. For this purpose, kidneys from nine cadavers were prepared for immunohistochemical staining and were supplemented with a fresh human kidney obtained by nephrectomy. TRPC6 was detected in glomeruli and in the parietal epithelial cells of Bowman’s capsule. Larger amounts were detected in the tubular system and collecting ducts. In contrast to the peritubular capillary bed, which showed no immune reaction, the cortical resistance vessels showed mild TRPC6 staining. In conclusion, our studies on the expression of TRPC6 in human kidney tissue support the translational concept of the involvement of TRPC6 in various renal diseases and reveal new aspects of the distribution of TRPC6 in the human kidney.
Keywords	TRPC6 ; human kidney ; glomeruli ; tubular system ; Computer applications to medicine. Medical informatics ; R858-859.7
Subject code	616
Language	English
Publishing date	2022-04-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: IL-17C and IL-17RE Promote Wound Closure in a Staphylococcus aureus -Based Murine Wound Infection Model

Linda Pätzold / Alexandra Stark / Felix Ritzmann / Carola Meier / Thomas Tschernig / Jörg Reichrath / Robert Bals / Markus Bischoff / Christoph Beisswenger

Microorganisms, Vol 9, Iss 1821, p

2021 Volume 1821

Abstract: The epithelial cytokine interleukin-17C (IL-17C) mediates inflammation through the interleukin 17 receptor E (IL-17RE). Prior studies showed a detrimental role of IL-17C in the pathogenesis of immune-mediated skin diseases (e.g., psoriasis). Here, we ... ...

Abstract	The epithelial cytokine interleukin-17C (IL-17C) mediates inflammation through the interleukin 17 receptor E (IL-17RE). Prior studies showed a detrimental role of IL-17C in the pathogenesis of immune-mediated skin diseases (e.g., psoriasis). Here, we examined the role of IL-17C/IL-17RE in wound closure in a Staphylococcus aureus wound infection model. We demonstrate that wound closure is significantly delayed in IL-17RE ( Il-17re −/− )- and 17C ( Il-17c −/− )-deficient mice. There was no significant difference between WT, Il-17re −/− , and Il-17c −/− mice in the absence of infection. Deficiency for IL-17RE and IL-17C did not significantly affect the elimination of bacteria. IL-17C expression was increased in the epidermis of human S. aureus -infected skin. Our results indicate that the IL-17C/IL-17RE axis contributes to the closure of infected wounds but does not contribute to the elimination of S. aureus .
Keywords	Staphylococcus aureus ; wound infection ; interleukin-17C ; wound closure ; Biology (General) ; QH301-705.5
Language	English
Publishing date	2021-08-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Human stem cells express pannexins

Nadine Hainz / Anja Beckmann / Madline Schubert / Alexandra Haase / Ulrich Martin / Thomas Tschernig / Carola Meier

BMC Research Notes, Vol 11, Iss 1, Pp 1-

2018 Volume 6

Abstract: Abstract Objective Pannexins are channel proteins important for the release of calcium and adenosine triphosphate, which are among other functions involved in early development. Here, the expression of pannexins was investigated in induced pluripotent ... ...

Abstract	Abstract Objective Pannexins are channel proteins important for the release of calcium and adenosine triphosphate, which are among other functions involved in early development. Here, the expression of pannexins was investigated in induced pluripotent stem cells derived from human cord blood endothelial cells (hCBiPS2), in hematopoietic stem cell-derived induced pluripotent stem cells (HSC_F1285_T-iPS2) and in human embryonic stem cells (HES-3). The expression of pannexin (Panx) 1–3 mRNAs was analyzed in all three undifferentiated stem cell lines. Stem cells then underwent undirected differentiation into embryoid bodies and were analyzed regarding expression of germ layer-specific genes. Results Panx1, Panx2, and Panx3 mRNAs were expressed in all undifferentiated stem cell lines investigated. In comparison, Panx1 showed the highest expression among all pannexins. The undirected differentiation resulted in a mixed germ layer genotype in all three stem cell lines. Whereas the expression of Panx1 was not affected by differentiation, the expression of Panx2 was slightly increased in differentiated hCBiPS2 cells, HSC_F1285_T-iPS2 as well as HES3 cells as compared to their undifferentiated counterparts. A slight increase of Panx3 expression was observed in differentiated hCBiPS2 cells only. In conclusion, pluripotent stem cells express all three pannexin genes.
Keywords	Pannexins ; Human stem cells ; Differentiation ; Endoderm ; Regulation ; Medicine ; R ; Biology (General) ; QH301-705.5 ; Science (General) ; Q1-390
Subject code	571
Language	English
Publishing date	2018-01-01T00:00:00Z
Publisher	BMC
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article: Toward Higher Sensitivity in Quantitative MALDI Imaging Mass Spectrometry of CNS Drugs Using a Nonpolar Matrix

Rzagalinski, Ignacy / Borislav Kovačević / Nadine Hainz / Carola Meier / Thomas Tschernig / Dietrich A. Volmer

Analytical chemistry. 2018 Sept. 27, v. 90, no. 21

2018

Abstract: Tissue-specific ion suppression is an unavoidable matrix effect in MALDI mass spectrometry imaging (MALDI-MSI), the negative impact of which on precision and accuracy in quantitative MALDI-MSI can be reduced to some extent by applying isotope internal ... ...

Abstract	Tissue-specific ion suppression is an unavoidable matrix effect in MALDI mass spectrometry imaging (MALDI-MSI), the negative impact of which on precision and accuracy in quantitative MALDI-MSI can be reduced to some extent by applying isotope internal standards for normalization and matrix-matched calibration routines. The detection sensitivity still suffers, however, often resulting in significant loss of signal for the investigated analytes. An MSI application considerably affected by this phenomenon is the quantitative spatial analysis of central nervous system (CNS) drugs. Most of these drugs are low molecular weight, lipophilic compounds, which exhibit inefficient desorption and ionization during MALDI using conventional polar acidic matrices (CHCA, DHB). Here, we present the application of the (2-[(2E)-3-(4-tert-butylphenyl)-2-methylprop-2-enylidene]malononitrile) matrix for high sensitivity imaging of CNS drugs in mouse brain sections. Since DCTB is usually described as an electron-transfer matrix, we provide a rationale (i.e., computational calculations of gas-phase proton affinity and ionization energy) for an additional proton-transfer ionization mechanism with this matrix. Furthermore, we compare the extent of signal suppression for five different CNS drugs when employing DCTB versus CHCA matrices. The results showed that the signal suppression was not only several times lower with DCTB than with CHCA but also depended on the specific tissue investigated. Finally, we present the application of DCTB and ultrahigh resolution Fourier transform ion cyclotron resonance mass spectrometry to quantitative MALDI imaging of the anesthetic drug xylazine in mouse brain sections based on a linear matrix-matched calibration curve. DCTB afforded up to 100-fold signal intensity improvement over CHCA when comparing representative single MSI pixels and >440-fold improvement for the averaged mass spectrum of the adjacent tissue sections.
Keywords	anesthetics ; brain ; calibration ; chemical species ; desorption ; detection limit ; electron transfer ; energy ; gases ; image analysis ; ionization ; isotopes ; lipophilicity ; matrix-assisted laser desorption-ionization mass spectrometry ; mice ; molecular weight ; xylazine
Language	English
Dates of publication	2018-0927
Size	p. 12592-12600.
Publishing place	American Chemical Society
Document type	Article
ZDB-ID	1508-8
ISSN	1520-6882 ; 0003-2700
ISSN (online)	1520-6882
ISSN	0003-2700
DOI	10.1021/acs.analchem.8b02740
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Probenecid arrests the progression of pronounced clinical symptoms in a mouse model of multiple sclerosis

Nadine Hainz / Sandra Wolf / Artjom Beck / Stefan Wagenpfeil / Thomas Tschernig / Carola Meier

Scientific Reports, Vol 7, Iss 1, Pp 1-

2017 Volume 9

Abstract: Abstract While it has been established that Probenecid (PBN) prevents the onset of experimental autoimmune encephalomyelitis (EAE) in mice, it is not clear whether it has any effect on already manifest EAE. The aim of this study was therefore to analyze ... ...

Abstract	Abstract While it has been established that Probenecid (PBN) prevents the onset of experimental autoimmune encephalomyelitis (EAE) in mice, it is not clear whether it has any effect on already manifest EAE. The aim of this study was therefore to analyze the therapeutic effect of PBN in pronounced EAE. Mice with manifest clinical symptoms of EAE were either treated with PBN or solvent for 20 days, or they were left untreated. The clinical symptoms were monitored daily. Inflammation, demyelination and oligodendrocyte numbers were determined in the spinal cord. We were able to demonstrate that PBN not only significantly prolonged survival but also prevented the progression of clinical symptoms in the EAE model of multiple sclerosis. In addition, we were able to show that PBN reduced inflammation, T cell infiltration and oligodendrocyte cell loss. PBN was previously shown to inhibit – among other targets – pannexin channels. As pannexin channels provide conduits for ATP, are associated with the inflammasome, and act as “find me-signals” in the process of apoptosis, inhibition of pannexins via PBN might contribute to the PBN-effects observed in this study. The beneficial and therapeutic effects of PBN in the context of EAE demonstrate an intriguing link between PBN and neuroinflammation, which might foster translational interest.
Keywords	Medicine ; R ; Science ; Q
Subject code	610
Language	English
Publishing date	2017-12-01T00:00:00Z
Publisher	Nature Publishing Group
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: First Genomic Analysis of Dendritic Cells from Lung and Draining Lymph Nodes in Murine Asthma

Thomas Tschernig / Christina Hartwig / Andreas Jeron / Quoc Thai Dinh / Marcus Gereke / Dunja Bruder

International Journal of Genomics, Vol

2015 Volume 2015

Keywords	Genetics ; QH426-470 ; Biology (General) ; QH301-705.5 ; Science ; Q
Language	English
Publishing date	2015-01-01T00:00:00Z
Publisher	Hindawi Publishing Corporation
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Controversial data on simvastatin in asthma

Thomas Tschernig / Wolfgang Bäumer / Reinhard Pabst

Journal of Asthma and Allergy, Vol 2010, Iss default, Pp 57-

What about the rat model?

2010 Volume 63

Abstract: Thomas Tschernig1, Wolfgang Bäumer2, Reinhard Pabst11Institute of Functional and Applied Anatomy, Hannover Medical School, Hannover, 2Institute of Pharmacology, Toxicology and Pharmacy, University of Veterinary Medicine, Hannover, GermanyAbstract: The ... ...

Abstract	Thomas Tschernig1, Wolfgang Bäumer2, Reinhard Pabst11Institute of Functional and Applied Anatomy, Hannover Medical School, Hannover, 2Institute of Pharmacology, Toxicology and Pharmacy, University of Veterinary Medicine, Hannover, GermanyAbstract: The effects of simvastatin on lung inflammation in asthma are controversial. Reduction of inflammation and hyperreactivity has been reported in studies using murine models of asthma. In contrast, a clinical study has not found beneficial effects in patients. The rat model of asthma has some distinct advantages and is still widely used in industrial studies. Therefore, the role of simvastatin was investigated in this rat model using intraperitoneal and intratracheal administration. With both simvastatin administration routes, the relative and absolute numbers of neutrophils, eosinophils, and lymphocytes were only partially reduced after increasing dosages (0.1, 1.0, and 10 mg per animal). The most obvious effect was on CD4 T cell numbers, which were reduced in most treatment groups. The results presented here suggest that treatment with simvastatin differs between species, and that it is too early for extrapolation of these data to humans.Keywords: simvastatin, inflammation, rat, asthma
Keywords	Immunologic diseases. Allergy ; RC581-607 ; Specialties of internal medicine ; RC581-951 ; Internal medicine ; RC31-1245 ; Medicine ; R ; DOAJ:Allergy and Immunology ; DOAJ:Medicine (General) ; DOAJ:Health Sciences
Subject code	610
Language	English
Publishing date	2010-07-01T00:00:00Z
Publisher	Dove Medical Press
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: ClpC affects the intracellular survival capacity of Staphylococcus aureus in non-professional phagocytic cells

Gubesh Gunaratnam / Lorena Tuchscherr / Mohamed I. Elhawy / Ralph Bertram / Janina Eisenbeis / Christian Spengler / Thomas Tschernig / Bettina Löffler / Greg A. Somerville / Karin Jacobs / Mathias Herrmann / Markus Bischoff

Scientific Reports, Vol 9, Iss 1, Pp 1-

2019 Volume 12

Abstract: Abstract Invasion and persistence of bacteria within host cells requires that they adapt to life in an intracellular environment. This adaptation induces bacterial stress through events such as phagocytosis and enhanced nutrient-restriction. During ... ...

Abstract	Abstract Invasion and persistence of bacteria within host cells requires that they adapt to life in an intracellular environment. This adaptation induces bacterial stress through events such as phagocytosis and enhanced nutrient-restriction. During stress, bacteria synthesize a family of proteins known as heat shock proteins (HSPs) to facilitate adaptation and survival. Previously, we determined the Staphylococcus aureus HSP ClpC temporally alters bacterial metabolism and persistence. This led us to hypothesize that ClpC might alter intracellular survival. Inactivation of clpC in S. aureus strain DSM20231 significantly enhanced long-term intracellular survival in human epithelial (HaCaT) and endothelial (EA.hy926) cell lines, without markedly affecting adhesion or invasion. This phenotype was similar across a genetically diverse collection of S. aureus isolates, and was influenced by the toxin/antitoxin encoding locus mazEF. Importantly, MazEF alters mRNA synthesis and/or stability of S. aureus virulence determinants, indicating ClpC may act through the mRNA modulatory activity of MazEF. Transcriptional analyses of total RNAs isolated from intracellular DSM20231 and isogenic clpC mutant cells identified alterations in transcription of α-toxin (hla), protein A (spa), and RNAIII, consistent with the hypothesis that ClpC negatively affects the intracellular survival of S. aureus in non-professional phagocytic cells, via modulation of MazEF and Agr.
Keywords	Medicine ; R ; Science ; Q
Language	English
Publishing date	2019-11-01T00:00:00Z
Publisher	Nature Publishing Group
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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