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https://www.readbyqxmd.com/read/28214865/inhibition-of-trpc6-signal-pathway-alleviates-podocyte-injury-induced-by-tgf-%C3%AE-1
#1
Haiting Huang, Yanwu You, Xu Lin, Chunrong Tang, Xiangjun Gu, Meiying Huang, Youling Qin, Junhua Tan, Feifan Huang
BACKGROUND/AIMS: Transforming growth factor beta 1 (TGF-β1) plays a critical role in the pathogenesis of glomerulosclerosis. The purpose of this study was to examine the effects of inhibition of transient receptor potential cation channel C6 (TRPC6) on podocyte injury induced by TGF-β1 via nephrin and desmin mechanisms. METHODS: A rat model of nephropathy was first induced by intravenous injections of adriamycin to determine TRPC6 signal pathway engaged in glomerulosclerosis in vivo...
January 18, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28210627/hyperforin-hp-%C3%AE-cyclodextrin-enhances-mechanosensitive-ca-2-signaling-in-hacat-keratinocytes-and-in-atopic-skin-ex-vivo-which-accelerates-wound-healing
#2
Hiroya Takada, Jun Yonekawa, Masami Matsumoto, Kishio Furuya, Masahiro Sokabe
Cutaneous wound healing is accelerated by mechanical stretching, and treatment with hyperforin, a major component of a traditional herbal medicine and a known TRPC6 activator, further enhances the acceleration. We recently revealed that this was due to the enhancement of ATP-Ca(2+) signaling in keratinocytes by hyperforin treatment. However, the low aqueous solubility and easy photodegradation impede the topical application of hyperforin for therapeutic purposes. We designed a compound hydroxypropyl-β-cyclodextrin- (HP-β-CD-) tetracapped hyperforin, which had increased aqueous solubility and improved photoprotection...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28204945/spectrum-of-mutations-in-chinese-children-with-steroid-resistant-nephrotic-syndrome
#3
Fang Wang, Yanqin Zhang, Jianhua Mao, Zihua Yu, Zhuwen Yi, Li Yu, Jun Sun, Xiuxiu Wei, Fangrui Ding, Hongwen Zhang, Huijie Xiao, Yong Yao, Weizhen Tan, Svjetlana Lovric, Jie Ding, Friedhelm Hildebrandt
BACKGROUND: The aim of this study was to elucidate whether genetic screening test results of pediatric patients with steroid-resistant nephrotic syndrome (SRNS) vary with ethnicity. METHODS: Using high-throughput DNA sequencing, 28 nephrotic syndrome-related genes were analyzed in 110 chil-dren affected by SRNS and 10 children with isolated proteinuria enrolled by 5 centers in China (67 boys, 53 girls). Their age at disease onset ranged from 1 day to 208 months (median, 48...
February 15, 2017: Pediatric Nephrology: Journal of the International Pediatric Nephrology Association
https://www.readbyqxmd.com/read/28124739/the-regulation-of-transient-receptor-potential-canonical-4-trpc4-channel-by-phosphodiesterase-5-inhibitor-via-the-cyclic-guanosine-3-5-monophosphate
#4
Jinhong Wie, SeungJoo Jeong, Misun Kwak, Jongyun Myeong, MeeRee Chae, Jong Kwan Park, Sung Won Lee, Insuk So
The transient receptor potential (TRP) protein superfamily consists of a diverse group of cation channels that bear structural similarities to the fruit fly Drosophila TRP. The TRP superfamily is distinct from other groups of ion channels in displaying a large diversity in ion selectivity, modes of activation, and physiological functions. Classical TRP (transient receptor potential canonical (TRPC)) channels are activated by stimulation of Gq-PLC-coupled receptors and modulated by phosphorylation. The cyclic guanosine monophosphate (cGMP)-PKG pathway is involved in the regulation of TRPC3 and TRPC6 channels...
January 26, 2017: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/28110963/hyperforin-activates-gene-transcription-involving-transient-receptor-potential-c6-channels
#5
Gerald Thiel, Oliver G Rössler
Hypericum perforatum is one of the most prominent medical plants. Hyperforin, a main ingredient of H. perforatum, has been shown to activate transient receptor potential canonical C6 (TRPC6) channels. Alternatively, it has been proposed that hyperforin functions as a protonophore in a TRPC6-independent manner. Here, we show that hyperforin stimulation activates the transcription factor AP-1 in HEK293 cells expressing TRPC6 (T6.11 cells), but did not substantially change the AP-1 activity in HEK293 cells lacking TRPC6...
January 19, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28107550/enhanced-trpc-channel-mediated-ca-2-influx-in-the-cells-with-phospholipase-c-%C3%AE-1-overexpression-its-possible-role-in-coronary-artery-spasm
#6
Kazuo Murakami, Tomohiro Osanai, Makoto Tanaka, Kimitaka Nishizaki, Takahiko Kinjo, Tomohiro Tanno, Yuji Ishida, Akiko Suzuki, Tomohide Endo, Hirofumi Tomita, Ken Okumura
We reported that coronary spasm was induced in the transgenic mice with the increased phospholipase C (PLC)-δ1 activity. We investigated the effect of enhanced PLC-δ1 on Ca(2+) influx and its underlying mechanisms. We used human embryonic kidney (HEK)-293 and coronary arteries-smooth-muscle cells (CASMC). Intracellular free Ca(2+) concentration ([Ca(2+) ]i ) (nM) was measured by fura-2, and Ca(2+) influx was evaluated by the increase in [Ca(2+) ]i after addition of extracellular Ca(2+) . Acetylcholine (ACh) was used to induce Ca(2+) influx...
January 20, 2017: Fundamental & Clinical Pharmacology
https://www.readbyqxmd.com/read/28077439/the-functional-expression-of-transient-receptor-potential-channels-in-the-mouse-endometrium
#7
Katrien De Clercq, Charlotte Van den Eynde, Aurélie Hennes, Rieta Van Bree, Thomas Voets, Joris Vriens
STUDY QUESTION: Does mouse endometrial epithelial cells and stromal cells have a similar transient receptor potential (TRP)-channel expression profile and to that found in the human endometrium? SUMMARY ANSWER: Mouse endometrial epithelial and stromal cells have a distinct TRP channel expression profile analogous to what has been found in human endometrium, and hence suggests the mouse a good model to investigate the role of TRP channels in reproduction. WHAT IS KNOWN ALREADY: An optimal intercellular communication between epithelial and stromal endometrial cells is crucial for successful reproduction...
January 6, 2017: Human Reproduction
https://www.readbyqxmd.com/read/28062998/high-glucose-enhances-isoflurane-induced-neurotoxicity-by-regulating-trpc-dependent-calcium-influx
#8
ZhongJie Liu, ChangQing Ma, Wei Zhao, QingGuo Zhang, Rui Xu, HongFei Zhang, HongYi Lei, ShiYuan Xu
Isoflurane is a commonly used inhalational anesthetic that can induce neurotoxicity via elevating cytosolic calcium (Ca(2+)). High glucose regulates the expression of a family of non-selective cation channels termed transient receptor potential canonical (TRPC) channels that may contribute to Ca(2+) influx. In the present study, we investigated whether high glucose enhances isoflurane-induced neurotoxicity by regulating TRPC-dependent Ca(2+) influx. First, we evaluated toxic damage in mice primary cultured hippocampal neurons and human neuroblastoma cells (SH-SY5Y cells) after hyperglycemia and isoflurane exposure...
January 6, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28039055/tgf%C3%AE-1-induces-stress-fiber-formation-through-upregulation-of-trpc6-in-vascular-smooth-muscle-cells
#9
Soonbum Park, Sanghoon Lee, Eun-Jung Park, MinJi Kang, Insuk So, Ju-Hong Jeon, Jung Nyeo Chun
Aberrant transforming growth factor β1 (TGFβ1) signaling plays a crucial role in the pathogenesis of vascular fibrosis. On the other hand, deregulated transient receptor potential canonical 6 (TRPC6) channel expression shows impaired vascular physiology and wound healing. However, it has little been known about the functional association between TGFβ1 and TRPC6 in vascular smooth muscle cells (VSMCs). In this study, we analyzed the microarray data obtained from TGFβ1-treated A7r5 VSMCs. We found that TGFβ1 specifically elevates the expression level of TRPC6 mainly through Smad-dependent canonical pathway...
January 29, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28034782/spinal-trpc6-channels-contributes-to-morphine-induced-antinociceptive-tolerance-and-hyperalgesia-in-rats
#10
Hua Jin, Ying-Tong Sun, Guang-Qiong Guo, Da-Lin Chen, Yu-Jin Li, Gao-Peng Xiao, Xin-Nan Li
The chronic administration of opioids results in the development of morphine analgesic tolerance and withdrawl-induced hyperalgesia, which limits their clinical utility in pain treatment. However, the cellular mechanisms underlying opioid-induced tolerance and hyperalgesia are not fully understood. The transient receptor potential canonical channel TRPC6 is important for brain development and function, as it regulates cytosolic, endoplasmic reticulum, and mitochondrial Ca(2+) levels in neural cells. Here, we report that TRPC6 expression in the spinal cord was up-regulated after chronic morphine treatment...
February 3, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28030826/inhibition-of-trpc6-reduces-non-small-cell-lung-cancer-cell-proliferation-and-invasion
#11
Li-Li Yang, Bing-Chen Liu, Xiao-Yu Lu, Yan Yan, Yu-Jia Zhai, Qing Bao, Paul W Doetsch, Xingming Deng, Tiffany L Thai, Abdel A Alli, Douglas C Eaton, Bao-Zhong Shen, He-Ping Ma
Recent studies indicate that the transient receptor potential canonical 6 (TRPC6) channel is highly expressed in several types of cancer cells. However, it remains unclear whether TRPC6 contributes to the malignancy of human non-small cell lung cancer (NSCLC). We used a human NSCLC A549 cell line as a model and found that pharmacological blockade or molecular knockdown of TRPC6 channel inhibited A549 cell proliferation by arresting cell cycle at the S-G2M phase and caused a significant portion of cells detached and rounded-up, but did not induce any types of cell death...
January 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/28028935/renoprotection-focus-on-trpv1-trpv4-trpc6-and-trpm2
#12
REVIEW
L Markó, M Mannaa, T N Haschler, S Krämer, M Gollasch
Members of the transient receptor potential (TRP) cation channel receptor family have unique sites of regulatory function in the kidney which enables them to promote regional vasodilatation and controlled Ca(2+) influx into podocytes and tubular cells. Activated TRP vanilloid 1 receptor channels (TRPV1) have been found to elicit renoprotection in rodent models of acute kidney injury following ischaemia/reperfusion. Transient receptor potential cation channel, subfamily C, member 6 (TRPC6) in podocytes is involved in chronic proteinuric kidney disease, particularly in focal segmental glomerulosclerosis (FSGS)...
March 2017: Acta Physiologica
https://www.readbyqxmd.com/read/27979597/inhibition-of-trpc6-channels-ameliorates-renal%C3%A2-fibrosis-and-contributes-to-renal-protection%C3%A2-by%C3%A2-soluble-klotho
#13
Yueh-Lin Wu, Jian Xie, Sung-Wan An, Noelynn Oliver, Nestor X Barrezueta, Mei-Hsiang Lin, Lutz Birnbaumer, Chou-Long Huang
Fibrosis is an exaggerated form of tissue repair that occurs with serious damage or repetitive injury and ultimately leads to organ failure due to the excessive scarring. Increased calcium ion entry through the TRPC6 channel has been associated with the pathogenesis of heart and glomerular diseases, but its role in renal interstitial fibrosis is unknown. We studied this by deletion of Trpc6 in mice and found it decreased unilateral ureteral obstruction-induced interstitial fibrosis and blunted increased mRNA expression of fibrosis-related genes in the ureteral obstructed kidney relative to that in the kidney of wild-type mice...
December 12, 2016: Kidney International
https://www.readbyqxmd.com/read/27960162/the-mtorc2-akt-nf%C3%AE%C2%BAb-pathway-mediated-activation-of-trpc6-participates-in-adriamycin-induced-podocyte-apoptosis
#14
Hai-Tao Zhang, Wei-Wei Wang, Li-Hong Ren, Xia-Xia Zhao, Zhi-Hui Wang, De-Li Zhuang, Yun-Nuo Bai
BACKGROUND/AIMS: Although increased expression and gain function of transient receptor potential cation channel 6 (TRPC6) has been associated with the pathogenesis of some proteinuric glomerular diseases, it remains elusive how TRPC6 participates in the process of podocyte damage. METHODS: The potential signaling responsible for TRPC6 activation was investigated using immunoblot assays in an in vitro podocyte injury model induced by Adriamycin (ADR). Podocyte apoptosis was measured using FITC-conjugated Annexin V and Propidium Iodide staining...
2016: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/27932059/classical-transient-receptor-potential-6-trpc6-channels-support-myofibroblast-differentiation-and-development-of-experimental-pulmonary-fibrosis
#15
Katharina Hofmann, Susanne Fiedler, Sarah Vierkotten, Jonas Weber, Stephan Klee, Jie Jia, Wolfgang Zwickenpflug, Veit Flockerzi, Ursula Storch, Ali Önder Yildirim, Thomas Gudermann, Melanie Königshoff, Alexander Dietrich
Pulmonary fibrosis (PF) is a chronic progressive lung disease without effective medical treatment options leading to respiratory failure and death within 3-5years of diagnosis. The pathological process of PF is driven by aberrant wound-healing involving fibroblasts and myofibroblasts differentiated by secreted profibrotic transforming growth factor β (TGF-β1). Classical transient receptor potential 6 (TRPC6), a Na(+)- and Ca(2+)-permeable cation channel, is able to promote myofibroblast conversion of primary rat cardiac and human dermal fibroblasts and TRPC6-deficiency impaired wound healing after injury...
February 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27895156/sildenafil-prevents-podocyte-injury-via-ppar-%C3%AE-mediated-trpc6-inhibition
#16
Ramon Sonneveld, Joost G Hoenderop, Andrea M Isidori, Carole Henique, Henry B Dijkman, Jo H Berden, Pierre-Louis Tharaux, Johan van der Vlag, Tom Nijenhuis
Transient receptor potential channel C6 (TRPC6) gain-of-function mutations and increased TRPC6 expression in podocytes induce glomerular injury and proteinuria. Sildenafil reduces TRPC6 expression and activity in nonrenal cell types, although the mechanism is unknown. Peroxisome proliferator-activated receptor γ (PPAR-γ) is a downstream target of sildenafil in the cyclic guanosine monophosphate (cGMP)-activated protein kinase G (PKG) axis. PPAR-γ agonists, like pioglitazone, appear antiproteinuric. We hypothesized that sildenafil inhibits TRPC6 expression in podocytes through PPAR-γ-dependent mechanisms, thereby counteracting podocyte injury and proteinuria...
November 28, 2016: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/27881772/store-operated-calcium-channel-complex-in-postsynaptic-spines-a-new-therapeutic-target-for-alzheimer-s-disease-treatment
#17
Hua Zhang, Suya Sun, Lili Wu, Ekaterina Pchitskaya, Olga Zakharova, Klementina Fon Tacer, Ilya Bezprozvanny
: Mushroom dendritic spine structures are essential for memory storage and the loss of mushroom spines may explain memory defects in aging and Alzheimer's disease (AD). The stability of mushroom spines depends on stromal interaction molecule 2 (STIM2)-mediated neuronal-store-operated Ca(2+) influx (nSOC) pathway, which is compromised in AD mouse models, in aging neurons, and in sporadic AD patients. Here, we demonstrate that the Transient Receptor Potential Canonical 6 (TRPC6) and Orai2 channels form a STIM2-regulated nSOC Ca(2+) channel complex in hippocampal mushroom spines...
November 23, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27879271/vitamin-d3-prevents-calcium-induced-progression-of-early-stage-prostate-tumors-by-counteracting-trpc6-and-calcium-sensing-receptor-upregulation
#18
Sophie Bernichtein, Natascha Pigat, Nicolas Barry Delongchamps, Florence Boutillon, Virginie Verkarre, Philippe Camparo, Edouard Reyes-Gomez, Arnaud Méjean, Stéphane M Oudard, Eve M Lepicard, Mélanie Viltard, Jean-Claude Souberbielle, Gérard Friedlander, Thierry Capiod, Vincent Goffin
Active surveillance has emerged as an alternative to immediate treatment for men with low-risk prostate cancer. Accordingly, identification of environmental factors that facilitate progression to more aggressive stages is critical for disease prevention. Although calcium-enriched diets have been speculated to increase prostate cancer risk, their impact on early-stage tumors remains unexplored. In this study, we addressed this issue with a large interventional animal study. Mouse models of fully penetrant and slowly evolving prostate tumorigenesis showed that a high calcium diet dramatically accelerated the progression of prostate intraepithelial neoplasia, by promoting cell proliferation, micro-invasion, tissue inflammation, and expression of acknowledged prostate cancer markers...
January 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/27874267/human-digital-meissner-corpuscles-display-immunoreactivity-for-the-multifunctional-ion-channels-trpc6-and-trpv4
#19
Paula Alonso-González, Roberto Cabo, Isabel San José, Angel Gago, Iván C Suazo, Olivia García-Suárez, Juan Cobo, José A Vega
Ion channels are at the basis of the sensory processes including mechanosensing. Some members of the transient receptor potential (TRP) ion channel superfamily have been proposed as mechanosensors, but their putative role in mechanotransduction is controversial. Among them there are TRP canonical 6 (TRPC6) and TRP vanilloid 4 (TRPV4) ion channels, which are known to cooperate in mechanical hyperalgesia. Here, we investigated the occurrence, distribution, and possible colocalization of TRPC6 and TRPV4 in human digital Meissner sensory corpuscles using immunohistochemistry and double immunofluorescence (associate with markers for specific corpuscular constituents)...
November 22, 2016: Anatomical Record: Advances in Integrative Anatomy and Evolutionary Biology
https://www.readbyqxmd.com/read/27865925/orai1-and-orai2-mediate-store-operated-calcium-entry-that-regulates-hl60-cell-migration-and-fak-phosphorylation
#20
R Diez-Bello, I Jardin, G M Salido, J A Rosado
Store-operated Ca(2+) entry (SOCE) is a major mechanism for the regulation of intracellular Ca(2+) homeostasis and cellular function. Emerging evidence has revealed that altered expression and function of the molecular determinants of SOCE play a critical role in the development or maintenance of several cancer hallmarks, including enhanced proliferation and migration. Here we show that, in the acute myeloid leukemia cell line HL60, Orai2 is highly expressed at the transcript level, followed by the expression of Orai1...
November 16, 2016: Biochimica et Biophysica Acta
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