scholarly journals P0421STUDY OF DIFFERENT EXPRESSION PROFILES OF “TRANSIENT RECEPTOR POTENTIAL ION CHANNEL (TRPC) GENE FAMILY” IN PATIENTS UNDERGOING RENAL BIOPSY WITH CLINICAL SUSPECTED GLOMERULONEPHRITIS

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Meltem Sezis ◽  
Yasemin Erac ◽  
Hale Güler ◽  
Gökhan Atay ◽  
Demirci Cenk ◽  
...  
Keyword(s):  
Intracellular Calcium ◽  
Renal Biopsy ◽  
Patient Group ◽  
Transient Receptor Potential ◽  
Expression Profiles ◽  
Receptor Potential ◽  
Control Group ◽  
Mrna Levels ◽  
Expression Levels ◽  
Transient Receptor

Abstract Background and Aims The transient receptor potential ion channels (TRPC) are non-selective Ca+ 2 permeable cation channels and are widely expressed in the tissues of vertebrates. They become active in response to signal transduction pathways associated with phospholipase C stimulation. TRPC6 is expressed in podocytes and is a component of the slit diaphragm. In genetic and acquired glomerular kidney diseases, TRPC6 overactivation causes podocyte damage by pathological Ca+ 2 entry. TRPC1, TRPC2, TRPC4, and TRPC5 interact with a protein called stromal-interacting molecule 1 (STIM 1), which is susceptible to intracellular calcium storage content. As a result of binding with this protein, TRPC channels bind to calcium-releasing zone in endosomes. The aim of the study was to investigate different expression profiles of TRPC family members in renal biopsy specimens in patients with clinically considered glomerulonephritis. Method This study was conducted with 108 patients admitted to Ege University Faculty of Medicine Nephrology Clinic who underwent a kidney biopsy with a preliminary diagnosis of glomerulonephritis and 37 patients who underwent a nephrectomy in urology clinic with a diagnosis of primary kidney tumour as a control case. PKD2, NPHS2, TRPC1, TRPC3, TRPC6, STIM-1 and Orai-1 mRNA levels were studied in the biopsy samples. Results When we compared the patient and the control group, the gender distribution of both groups was similar. The frequency of diabetes and hypertension was similar. The control group was statistically significantly older and glomerular filtration rates were higher than the patient group. In pathological examination, glomerulonephritis (57.5%) was diagnosed in the majority of patients. The most common etiologic factors were membranous nephropathy 23.1%, IgA nephropathy 13%, Amyloidosis 11.2%, focal segmental glomerulosclerosis 7.1%, proliferative glomerulonephritis 4.6%, minimal change disease 2.8% and membranoproliferative glomerulonephritis was 1.9%. 7.4% of the patients were diagnosed with diabetic nephropathy by renal biopsy. When we compared the TRPC expression profiles of the patient and the control group, the TRPC1, TRPC6, PKD2, NPHS2, STIM-1 and ORAi-1 mRNA levels of the patient group were statistically significantly higher than those of the control group (Figure). In contrast, TRPC3 mRNA levels were significantly lower in the patient group compared to the control group. When we performed subgroup analysis, the TRPC1, TRPC6 and STIM1 levels of the diabetic group were statistically significantly higher compared to the non-diabetic group of patients. We could not find any difference between TRPC expression profiles between the patients according to pathological diagnosis. Similarly, there was no difference between the amount of proteinuria (nephrotic level versus nephritic level). In correlation analysis, there was a negative correlation with TRPC6 and STIM1 levels with positive C4d staining of glomeruli in renal biopsy. Positive correlation was found between ORAI and glomerular sclerosis rate. Conclusion As a result, we found that other than TRPC3 mRNA level, other TRPC and related protein channels mRNA levels were statistically significantly increased in proteinuric kidney patients compared to healthy kidney tissue. We did not find a positive relationship between proteinuria severity and TRPC expression profiles. We found that TRPC6 and STIM1 expression levels were increased in diabetic patients, which supports the knowledge that intracellular calcium pathways were activated in podocyte damage. In our study, there were significantly increased STIM1 and ORAi-1 expression levels in proteinuric patients compared to the control group and their increase was closely related to TRPC6. From this we can conclude that these proteins play an important role in proteinuric kidney damage.

scholarly journals Preventive Effects of Different Fermentation Times of Shuidouchi on Diphenoxylate-Induced Constipation in Mice

Foods ◽  
2019 ◽  
Vol 8 (3) ◽  
pp. 86 ◽  
Author(s):  
Lianhong Chen ◽  
Jing Zhang ◽  
Huayi Suo ◽  
Wei Wang ◽  
Hongwei Wang ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Mrna Expression ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Normal Group ◽  
Control Group ◽  
Expression Levels ◽  
Transient Receptor ◽  
Oxide Synthase

This study compares the prevention effects of Shuidouchi with different fermentation times on constipation in mice. Shuidouchi is a short-time fermented soybean product. By improving its processing technology, it can incur better biological activity and become a health food. The Shuidouchi-treated mice were evaluated using constipation-related kits, quantitative polymerase chain reaction (qPCR), and Western blot assays. After the mice were fed 72-h-fermented Shuidouchi (72-SDC) for 9 d, the defecation time to excrete the first black stool was lower than that of the control and 24-SDC and 48-SDC groups, but was much higher than that of the normal group. The gastrointestinal (GI) transit of the small intestine of the 72-SDC group was higher than that of the control and the 24-SDC and 48-SDC groups, but lower that of the normal group. Meanwhile, 72-SDC could significantly increase the levels of ghrelin, endothelin-1 (ET-1), vasoactive intestinal peptide (VIP), and acetylcholinesterase (AchE) in the serum of constipated mice compared to the levels in mice in the control group. Moreover, 72-SDC could raise c-Kit, stem cell factor (SCF), glial cell-derived neurotrophic factor (GNDF), neuronal nitric oxide synthase (nNOS), and endothelial nitric oxide synthase (eNOS) messenger RNA (mRNA) and protein expression levels, and reduce transient receptor potential cation channel subfamily V member 1 (TRPV1) and inducible nitric oxide synthase (iNOS) expression levels in small-intestinal tissue compared to the levels in the control group. Meanwhile, 72-SDC also raised ghrelin mRNA expression in gastric tissue and transient receptor potential ankyrin 1 (TRPA1) mRNA expression in colon tissue compared to the control group mice; these effects were stronger than those of 24-SDC and 48-SDC. Shuidouchi has good preventative effects on constipation and performs best when fermented for at least 72 h.

scholarly journals Function of the Porcine TRPC1 Gene in Myogenesis and Muscle Growth

Cells ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 147
Author(s):  
Yu Fu ◽  
Peng Shang ◽  
Bo Zhang ◽  
Xiaolong Tian ◽  
Ruixue Nie ◽  
...  
Keyword(s):  
Transient Receptor Potential ◽  
Growth Traits ◽  
Expression Profiles ◽  
Muscle Growth ◽  
Receptor Potential ◽  
Transient Receptor Potential Channel ◽  
Nucleotide Polymorphisms ◽  
Pig Breeds ◽  
Muscle Tissues ◽  
Transient Receptor

In animals, muscle growth is a quantitative trait controlled by multiple genes. Previously, we showed that the transient receptor potential channel 1 (TRPC1) gene was differentially expressed in muscle tissues between pig breeds with divergent growth traits base on RNA-seq. Here, we characterized TRPC1 expression profiles in different tissues and pig breeds and showed that TRPC1 was highly expressed in the muscle. We found two single nucleotide polymorphisms (SNPs) (C-1763T and C-1604T) in TRPC1 that could affect the promoter region activity and regulate pig growth rate. Functionally, we used RNAi and overexpression to illustrate that TRPC1 promotes myoblast proliferation, migration, differentiation, fusion, and muscle hypertrophy while inhibiting muscle degradation. These processes may be mediated by the activation of Wnt signaling pathways. Altogether, our results revealed that TRPC1 might promote muscle growth and development and plays a key role in Wnt-mediated myogenesis.

scholarly journals Antinociceptive Effects of Emodin on CFA-Induced Inflammatory Pain in Rats

2020 ◽  
Vol 15 (7) ◽  
pp. 1934578X2094200
Author(s):  
Wan Ni ◽  
Nianyun Wang ◽  
Shenglan Tian ◽  
Qingbang Xu
Keyword(s):  
Mrna Expression ◽  
Inflammatory Pain ◽  
Transient Receptor Potential ◽  
Interleukin 1 ◽  
Receptor Potential ◽  
Enzyme Linked Immunosorbent Assay ◽  
Control Group ◽  
Transient Receptor Potential Vanilloid ◽  
Tnf Α ◽  
Transient Receptor

The effect of emodin on complete Freund’s adjuvant (CFA)-induced inflammatory pain in rats and its potential molecular mechanism was investigated. For this, a rat model of inflammatory pain induced by CFA was established and rats were treated with emodin by intraperitoneal injection. The pain threshold was evaluated by the von Frey, thermo hyperalgesia, and cold plate tests. The mRNA expression of transient receptor potential channel ankyrin type-1 ( Trpa1) and transient receptor potential vanilloid 1 ( Trpv1) was detected by quantitative reverse transcription polymerase chain reaction, and the level of inflammatory cytokines was determined by enzyme-linked immunosorbent assay. The mechanical and thermal pain thresholds of CFA-treated rats were significantly lower than those of the control rats, while the paw withdrawal responses in response to cold stimulation were higher than that of the control group. Emodin treatment significantly improved CFA-induced hyperalgesia. Further results showed that emodin inhibits the upregulation of Trpa1 and Trpv1 mRNA expression in the dorsal root ganglion (DRG) of rats with inflammatory pain compared with the control group. Emodin also significantly reduced the levels of tumor necrosis factor alpha (TNF-α), interleukin 1 beta (IL-1β), and interleukin 6 (IL-6) in the serum of rats with inflammatory pain. Thus, emodin may inhibit hyperalgesia induced by inflammatory stimulation by downregulating the mRNA expression of Trpa1 and Trpv1 in DRG neurons and reducing the levels of TNF-α, IL-1β, and IL-6.

scholarly journals Elucidation of a TRPC6-TRPC5 Channel Cascade That Restricts Endothelial Cell Movement

2008 ◽  
Vol 19 (8) ◽  
pp. 3203-3211 ◽  
Author(s):  
Pinaki Chaudhuri ◽  
Scott M. Colles ◽  
Manjunatha Bhat ◽  
David R. Van Wagoner ◽  
Lutz Birnbaumer ◽  
...  
Keyword(s):  
Intracellular Calcium ◽  
Calcium Concentration ◽  
Transient Receptor Potential ◽  
Calcium Influx ◽  
Cell Movement ◽  
Receptor Potential ◽  
Receptor Activation ◽  
Calcium Stores ◽  
Trpc Channels ◽  
Transient Receptor

Canonical transient receptor potential (TRPC) channels are opened by classical signal transduction events initiated by receptor activation or depletion of intracellular calcium stores. Here, we report a novel mechanism for opening TRPC channels in which TRPC6 activation initiates a cascade resulting in TRPC5 translocation. When endothelial cells (ECs) are incubated in lysophosphatidylcholine (lysoPC), rapid translocation of TRPC6 initiates calcium influx that results in externalization of TRPC5. Activation of this TRPC6–5 cascade causes a prolonged increase in intracellular calcium concentration ([Ca2+]i) that inhibits EC movement. When TRPC5 is down-regulated with siRNA, the lysoPC-induced rise in [Ca2+]i is shortened and the inhibition of EC migration is lessened. When TRPC6 is down-regulated or EC from TRPC6−/− mice are studied, lysoPC has minimal effect on [Ca2+]i and EC migration. In addition, TRPC5 is not externalized in response to lysoPC, supporting the dependence of TRPC5 translocation on the opening of TRPC6 channels. Activation of this novel TRPC channel cascade by lysoPC, resulting in the inhibition of EC migration, could adversely impact on EC healing in atherosclerotic arteries where lysoPC is abundant.

117 THE REGULATOR OF THE UTERINE TRPV6 GENE DURING PREGNANCY IN RODENTS

2008 ◽  
Vol 20 (1) ◽  
pp. 138
Author(s):  
B.-M. Lee ◽  
G.-S. Lee ◽  
E.-B. Jeung
Keyword(s):  
Transient Receptor Potential ◽  
Embryo Implantation ◽  
Receptor Potential ◽  
Reproductive Organs ◽  
Mrna Levels ◽  
Pregnant Rats ◽  
Ru 486 ◽  
Transient Receptor ◽  
Dunnett's Test ◽  
Hormone Antagonists

Transient receptor potential cation channel, subfamily V, member 6 (TRPV6) is an epithelial Ca2+ channel protein expressed in calcium-absorbing organs. Recently it was reported that TRPV6 is expressed in female reproductive organs. The present study was performed to investigate the expression and regulation of uterine and placental TRPV6 during gestation in rats. In the uterus, TRPV6 was moderately expressed at pregnancy day (P) 0 and decreased until P4. Its expression level then peaked at P5, implying that TRPV6 may be involved in embryo implantation. Around P13, uterine TRPV6 expression increased slightly a second time, and then gradually decreased until the end of pregnancy at P21. Tissue localization of TRPV6 expression was determined by immunohistochemistry methods. TRPV6 protein was detected in uterine endothelium layers and glands; however, it was not detected in uterine tissues attached to the placenta. In the placenta, TRPV6 mRNA levels increased in mid-gestation, and the tissue distribution of placental TRPV6 protein suggests that it may play a role in transferring calcium to the fetus during pregnancy. To investigate the pathway(s) mediating TRPV6 expression during pregnancy in rats and mice, steroid hormone antagonists ICI 182 780 (ICI) and RU 486 (RU) were injected prior to maximal TRPV6 expression, as anti-estrogen and anti-progesterone agents, respectively. Pregnant rats (P4 for uterine RNA preparation, P19 for placental RNA preparation) received subcutaneous injections of RU (2.5 mg per rat), ICI (0.5 mg per rat), or a combination of RU and ICI. In addition, ICR-mice at P9 were injected with RU (25 µg per mouse) and/or ICI (2 µg per mouse). We measured level of TRPV6 mRNA transcription using semi-quantitative RT-PCR and real-time PCR. Data were analyzed by nonparametric one-way analysis of variance using the Kruskal-Wallis test, followed by Dunnett's test for multiple comparisons to vehicle. In rats, TRPV6 expression was reduced by RU treatment, and in mice ICI treatment blocked TRPV6 expression. Taken together, these results suggest that progesterone in rats and estrogen in mice act to regulate TRPV6 expression in the uterus and placenta during pregnancy. In conclusion, TRPV6 may play a role in embryo implantation in the uterus and in calcium transport between embryo and mother in the placenta.

185 TRANSIENT RECEPTOR POTENTIAL CHANNEL-2 (TRPP2) REGULATES MOTILITY AND INTRACELLULAR CALCIUM OF PORCINE SPERM

2016 ◽  
Vol 28 (2) ◽  
pp. 223
Author(s):  
B. W. Daigneault ◽  
D. J. Miller
Keyword(s):  
Membrane Protein ◽  
Intracellular Calcium ◽  
Transient Receptor Potential ◽  
Beat Frequency ◽  
Receptor Potential ◽  
Transient Receptor Potential Channel ◽  
Sperm Function ◽  
Cystic Kidneys ◽  
Mammalian Sperm ◽  
Transient Receptor

Transient receptor potential channel-2 (TRPP2) is a membrane protein important for the regulation of calcium homeostasis in renal epithelial cells. Mutations in human TRPP2 cause enlarged cystic kidneys and contribute to polycystic kidney disease. In addition, TRPP2 functions have been described in some invertebrate sperm and are related to sperm-egg interactions and mating. Male Drosophila with mutated TRPP2 display a mild sperm motility phenotype but have a drastic reduction in fertility due to failed sperm migration and storage within the female tract. Although TRPP2 has critical roles for Drosophila sperm function, the protein has not been described in mammalian sperm. The TRPP2 mutations affecting sperm function could explain idiopathic subfertility that is not detected when evaluating sperm by routine analyses. Herein we report the location of TRPP2 in porcine sperm and have identified functions of TRPP2 in regulating sperm functions important for fertility. The TRPP2 was detected as a 110-kDa band in protein lysates from sperm after capacitation or mock incubation in conditions that do not capacitate sperm. With immunofluorescence, TRPP2 was most abundant on the head and principal piece of sperm with more consistent staining patterns when sperm were maintained in non-capacitating medium. Inhibition of TRPP2 by antiserum resulted in a reduction in sperm average path and curvilinear velocity and an increase in tail cross-beat frequency when sperm were incubated in capacitating conditions. Sperm incubated with TRPP2 antiserum also had a significant decrease in intracellular calcium concentration compared with control samples and failed to undergo an increase in calcium over 90 min that is characteristic of capacitating sperm. TRPP2 is a previously unreported mammalian sperm membrane protein that appears to function as an ion channel to regulate calcium and capacitation-like changes in porcine sperm. This project is supported by Agriculture and Food Research Initiative Competitive Grant no. 2011–67015–20099 and 2015–67015–23228 from the USDA National Institute of Food and Agriculture.

scholarly journals TRPV4 channels augment macrophage activation and ventilator-induced lung injury

2010 ◽  
Vol 299 (3) ◽  
pp. L353-L362 ◽  
Author(s):  
Kazutoshi Hamanaka ◽  
Ming-Yuan Jian ◽  
Mary I. Townsley ◽  
Judy A. King ◽  
Wolfgang Liedtke ◽  
...  
Keyword(s):  
Intracellular Calcium ◽  
Alveolar Macrophages ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Transient Receptor Potential Vanilloid ◽  
Cross Sectional ◽  
Ventilator Induced Lung Injury ◽  
Immunohistochemistry Staining ◽  
Permeability Increase ◽  
Transient Receptor

We have previously implicated transient receptor potential vanilloid 4 (TRPV4) channels and alveolar macrophages in initiating the permeability increase in response to high peak inflation pressure (PIP) ventilation. Alveolar macrophages were harvested from TRPV4−/− and TRPV4+/+ mice and instilled in the lungs of mice of the opposite genotype. Filtration coefficients ( Kf) measured in isolated perfused lungs after ventilation with successive 30-min periods of 9, 25, and 35 cmH2O PIP did not significantly increase in lungs from TRPV4−/− mice but increased >2.2-fold in TRPV4+/+ lungs, TRPV4+/+ lungs instilled with TRPV4−/− macrophages, and TRPV4−/− lungs instilled with TRPV4+/+ macrophages after ventilation with 35 cmH2O PIP. Activation of TRPV4 with 4-α-phorbol didecanoate (4αPDD) significantly increased intracellular calcium, superoxide, and nitric oxide production in TRPV4+/+ macrophages but not TRPV4−/− macrophages. Cross-sectional areas increased nearly 3-fold in TRPV4+/+ macrophages compared with TRPV4−/− macrophages after 4αPDD. Immunohistochemistry staining of lung tissue for nitrotyrosine revealed increased amounts in high PIP ventilated TRPV4+/+ lungs compared with low PIP ventilated TRPV4+/+ or high PIP ventilated TRPV4−/− lungs. Thus TRPV4+/+ macrophages restored susceptibility of TRPV4−/− lungs to mechanical injury. A TRPV4 agonist increased intracellular calcium and reactive oxygen and nitrogen species in harvested TRPV4+/+ macrophages but not TRPV4−/− macrophages. Kf increases correlated with tissue nitrotyrosine, a marker of peroxynitrite production.

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