scholarly journals Transient Receptor Potential Channel 6 Knockout Ameliorates Kidney Fibrosis by Inhibition of Epithelial–Mesenchymal Transition

2021 ◽  
Vol 8 ◽  
Author(s):  
Yanhong Zhang ◽  
Nina Yin ◽  
Anbang Sun ◽  
Qifang Wu ◽  
Wenzhu Hu ◽  
...  
Keyword(s):  
Transient Receptor Potential ◽  
Epithelial Mesenchymal Transition ◽  
Kidney Diseases ◽  
Receptor Potential ◽  
Transient Receptor Potential Channel ◽  
Kidney Fibrosis ◽  
Mesenchymal Transition ◽  
Transient Receptor ◽  
End Stage ◽  
The Relationship

Kidney fibrosis is generally confirmed to have a significant role in chronic kidney disease, resulting in end-stage kidney failure. Epithelial–mesenchymal transition (EMT) is an important molecular mechanism contributing to fibrosis. Tubular epithelial cells (TEC), the major component of kidney parenchyma, are vulnerable to different types of injuries and are a significant source of myofibroblast by EMT. Furthermore, TRPC6 knockout plays an anti-fibrotic role in ameliorating kidney damage. However, the relationship between TRPC6 and EMT is unknown. In this study, TRPC6−/− and wild-type (WT) mice were subjected to a unilateral ureteric obstruction (UUO) operation. Primary TEC were treated with TGF-β1. Western blot and immunofluorescence data showed that fibrotic injuries alleviated with the inhibition of EMT in TRPC6−/− mice compared to WT mice. The activation of AKT-mTOR and ERK1/2 pathways was down-regulated in the TRPC6−/− mice, while the loss of Na+/K+-ATPase and APQ1 was partially recovered. We conclude that TRPC6 knockout may ameliorate kidney fibrosis by inhibition of EMT through down-regulating the AKT-mTOR and ERK1/2 pathways. This could contribute to the development of effective therapeutic strategies on chronic kidney diseases.

scholarly journals PRP4 Promotes Skin Cancer by Inhibiting Production of Melanin, Blocking Influx of Extracellular Calcium, and Remodeling Cell Actin Cytoskeleton

2021 ◽  
Vol 22 (13) ◽  
pp. 6992
Author(s):  
Muhammad Bilal Ahmed ◽  
Salman Ul Islam ◽  
Young Sup Lee
Keyword(s):  
Drug Resistance ◽  
Actin Cytoskeleton ◽  
Transient Receptor Potential ◽  
Epithelial Mesenchymal Transition ◽  
Receptor Potential ◽  
Extracellular Calcium ◽  
Melanin Biosynthesis ◽  
Mesenchymal Transition ◽  
B16f10 Cells ◽  
Transient Receptor

Pre-mRNA processing factor 4B (PRP4) has previously been shown to induce epithelial-mesenchymal transition (EMT) and drug resistance in cancer cell lines. As melanin plays an important photoprotective role in the risk of sun-induced skin cancers, we have investigated whether PRP4 can induce drug resistance and regulate melanin biosynthesis in a murine melanoma (B16F10) cell line. Cells were incubated with a crucial melanogenesis stimulator, alpha-melanocyte-stimulating hormone, followed by transfection with PRP4. This resulted in the inhibition of the production of melanin via the downregulation of adenylyl cyclase-cyclic adenosine 3’,5’-monophosphate (AC)–(cAMP)–tyrosinase synthesis signaling pathway. Inhibition of melanin production by PRP4 leads to the promotion of carcinogenesis and induced drug resistance in B16F10 cells. Additionally, PRP4 overexpression upregulated the expression of β-arrestin 1 and desensitized the extracellular calcium-sensing receptor (CaSR), which in turn, inhibited the influx of extracellular Ca2+ ions. The decreased influx of Ca2+ was confirmed by a decreased expression level of calmodulin. We have demonstrated that transient receptor potential cation channel subfamily C member 1 was involved in the influx of CaSR-induced Ca2+ via a decreasing level of its expression. Furthermore, PRP4 overexpression downregulated the expression of AC, decreased the synthesis of cAMP, and modulated the actin cytoskeleton by inhibiting the expression of Ras homolog family member A (RhoA). Our investigation suggests that PRP4 inhibits the production of melanin in B16F10 cells, blocks the influx of Ca2+ through desensitization of CaSR, and modulates the actin cytoskeleton through downregulating the AC–cAMP pathway; taken together, these observations collectively lead to the promotion of skin carcinogenesis.

Overexpression of TrpC5 promotes tumor metastasis via the HIF-1α–Twist signaling pathway in colon cancer

2017 ◽  
Vol 131 (19) ◽  
pp. 2439-2450 ◽  
Author(s):  
Zhen Chen ◽  
Yaodan Zhu ◽  
Yongfei Dong ◽  
Peng Zhang ◽  
Xiping Han ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Cancer Cells ◽  
Signaling Pathway ◽  
Tumor Metastasis ◽  
Transient Receptor Potential ◽  
Epithelial Mesenchymal Transition ◽  
Hypoxia Inducible Factor ◽  
Receptor Potential ◽  
Transient Receptor Potential Channel ◽  
Mesenchymal Transition

In cancer cells, intracellular Ca2+ homeostasis is altered, and this is involved in tumor initiation, progression, and metastasis. However, little is known about the underlying mechanisms. Here, we report that transient receptor potential channel 5 (TrpC5), a receptor-activated non-selective Ca2+ channel, is correlated with tumor metastasis in colon cancer patients. Moreover, in colon cancer cells, overexpression of TrpC5 caused a robust rise in the concentration of ([Ca2+]i), decreased E-cadherin, and increased mesenchymal biomarker expression, then promoted cell migration, invasion, and proliferation. Interestingly, we found that TrpC5 mediated hypoxia-inducible factor 1α (HIF-1α) expression, activating Twist to promote the epithelial–mesenchymal transition (EMT). Notably, patients with high expression of TrpC5 displayed poorer overall and metastasis-free survival. Taken together, our findings demonstrate that TrpC5 induces the EMT through the HIF-1α–Twist signaling pathway to promote tumor metastasis in colon cancer.

scholarly journals Dexamethasone Resisted Podocyte Injury via Stabilizing TRPC6 Expression and Distribution

2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
Author(s):  
Shengyou Yu ◽  
L. Yu
Keyword(s):  
Mrna Expression ◽  
Transient Receptor Potential ◽  
Kidney Diseases ◽  
Receptor Potential ◽  
Transient Receptor Potential Channel ◽  
Protein Distribution ◽  
Puromycin Aminonucleoside ◽  
Differentiated Cells ◽  
Filtration Barrier ◽  
Transient Receptor

TRPC6, a member of the canonical transient receptor potential channel (TRPC) subfamily, is an important cation selective ion channel on podocytes. Podocytes are highly differentiated cells located on the visceral face of glomerular basement membrane and featured by numerous foot processes, on which nephrin, podocin, and TRPC6 locate. Podocytes and the slit diaphragm (SD) between adjacent foot processes form a selective filtration barrier impermeable to proteins. TRPC6 is very critical for normal podocyte function. To investigate the function of TRPC6 in podocytes and its relation to proteinuria in kidney diseases, we over-expressed TRPC6 in podocytes by puromycin aminonucleoside (PAN) and observed the changes of foot processes, TRPC6 protein distribution, and mRNA expression. Accordingly, in this study, we further investigated the role of specific signaling mechanisms underlying the prosurvival effects of dexamethasone (DEX) on podocyte repair. Our results showed that podocytes processes of overexpressing TRPC6 were reduced remarkably. These changes could be rescued by DEX via blocking TRPC6 channel. Additionally, our results also showed an improvement in TRPC6 arrangement in the cells and decrease of mRNA expression and protein distribution. From these results, we therefore proposed that overexpression of TRPC6 in podocytes may be one of the fundamental changes relating to the dysfunction of the SD and proteinuria. DEX may be maintained the structure and function integrity of SD by blocking TRPC6 signal pathway and played an important role in mechanisms of anti-proteinuria.

scholarly journals Evaluation of podocyte Rac-1 induced kidney disease by modulation of TRPC5

2021 ◽  
Author(s):  
Jochen Reiser ◽  
Onur K Polat ◽  
Elena Isaeva ◽  
Ke Zhu ◽  
Manuel Noben ◽  
...  
Keyword(s):  
Transgenic Mouse ◽  
Transient Receptor Potential ◽  
Kidney Diseases ◽  
Receptor Potential ◽  
Transient Receptor Potential Channel ◽  
Dominant Negative ◽  
Podocyte Injury ◽  
Chronic Kidney Diseases ◽  
Double Transgenic Mouse ◽  
Transient Receptor

Background Transient receptor potential channel 5 (TRPC5) is a non-selective cationic ion channel expressed in brain, kidney and other organs where its activation underlies podocyte injury in chronic kidney diseases. Specifically, it has been suggested that a podocyte TRPC5 plasma membrane relocation and channel activation following injury results from activation of Rac-1, propagating podocyte dysfunction and proteinuria. However, previous TRPC5 transgenic mouse studies had questioned a pathogenic role for TRPC5 in podocytes. This investigation was designed to specifically evaluate podocyte Rac-1 activation in the context of functional TRPC5 or a TRPC5 pore mutant to assess effects on proteinuria. Materials and Methods We employed single cell patch-clamp studies of cultured podocytes and studied proteinuria in transgenic mouse models to characterize the effects of TRPC5 following podocyte Rac-1 activation. Results Inhibition of TRPC5 by small molecules reportedly ameliorated proteinuria in murine models of proteinuric kidney diseases. In order to directly examine TRPC5 function following Rac-1-induced podocyte injury, we analyzed TRPC5 inhibition in podocyte specific Rac-1 (active) transgenic mice. In addition, we generated a double-transgenic mouse constitutively overexpressing either TRPC5 (TRPC5WT) or a TRPC5 dominant-negative pore mutant (TRPC5DN) in concert with podocyte specific and inducible activation of active Rac-1 (Rac-1Dtg). In electrophysiological experiments, active TRPC5 was detected in primary podocytes overexpressing TRPC5 but not in podocytes with endogenous TRPC5 expression, nor with Rac-1 overexpressing podocytes. TRPC5 inhibition did not change proteinuria in mice with active podocyte Rac-1, nor did an increase or loss of TRPC5 activity affected podocyte injury in Rac-1Dtg animals. Administration of TRPC5 inhibitors, ML204 and AC1903, did not alleviate podocyte Rac-1 induced proteinuria. Conclusion TRPC5 inhibition did not modify podocyte Rac-1 induced proteinuria in mice.

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.

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