Calcium-Activated Cl− Channel: Insights on the Molecular Identity in Epithelial Tissues

Rottgen, Trey; Nickerson, Andrew; Rajendran, Vazhaikkurichi M.

doi:10.3390/ijms19051432

Cited by 10 publications

(5 citation statements)

References 76 publications

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“…This is an in vitro investigation, and the drug was not tested in in vivo animal models. Previously published work using CFTR −/- mice demonstrated only a mild pathology, which was in opposition to the observed disease in humans, and this may be due to substantial amounts of CaCC anion secretion in mice [41] , [42] . Further studies will include evaluation in human sinonasal or bronchial cells in vitro and ex vivo and assessment of RGAE-mediated effects on CF murine and rat animal models [43] , [44] .…”

Section: Discussionmentioning

confidence: 64%

Korean Red Ginseng aqueous extract improves markers of mucociliary clearance by stimulating chloride secretion

Cho

Skinner

Zhang

et al. 2021

Journal of Ginseng Research

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Section: Discussionmentioning

confidence: 64%

Korean Red Ginseng aqueous extract improves markers of mucociliary clearance by stimulating chloride secretion

Cho

Skinner

Zhang

et al. 2021

Journal of Ginseng Research

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“…Depending on the cell type, swelling-induced Ca 2+ release will activate TMEM16 proteins and CFTR (Thiele et al, 1998;Wanitchakool et al, 2016), which parallels activation of VRAC. This circumstance may explain many earlier findings, such as the overlapping Cl − channel pharmacology (Koslowsky et al, 1994;Rottgen et al, 2018;Centeio et al, 2020).…”

Section: Discussionmentioning

confidence: 75%

Ca2+ Dependence of Volume-Regulated VRAC/LRRC8 and TMEM16A Cl– Channels

Centeio

Ousingsawat

Schreiber

et al. 2020

Front. Cell Dev. Biol.

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All vertebrate cells activate Cl– currents (ICl,swell) when swollen by hypotonic bath solution. The volume-regulated anion channel VRAC has now been identified as LRRC8/SWELL1. However, apart from VRAC, the Ca2+-activated Cl– channel (CaCC) TMEM16A and the phospholipid scramblase and ion channel TMEM16F were suggested to contribute to cell swelling-activated whole-cell currents. Cell swelling was shown to induce Ca2+ release from the endoplasmic reticulum and to cause subsequent Ca2+ influx. It is suggested that TMEM16A/F support intracellular Ca2+ signaling and thus Ca2+-dependent activation of VRAC. In the present study, we tried to clarify the contribution of TMEM16A to ICl,swell. In HEK293 cells coexpressing LRRC8A and LRRC8C, we found that activation of ICl,swell by hypotonic bath solution (Hypo; 200 mosm/l) was Ca2+ dependent. TMEM16A augmented the activation of LRRC8A/C by enhancing swelling-induced local intracellular Ca2+ concentrations. In HT29 cells, knockdown of endogenous TMEM16A attenuated ICl,swell and changed time-independent swelling-activated currents to VRAC-typical time-dependent currents. Activation of ICl,swell by Hypo was attenuated by blocking receptors for inositol trisphosphate and ryanodine (IP3R; RyR), as well as by inhibiting Ca2+ influx. The data suggest that TMEM16A contributes directly to ICl,swell as it is activated through swelling-induced Ca2+ increase. As activation of VRAC is shown to be Ca2+-dependent, TMEM16A augments VRAC currents by facilitating Hypo-induced Ca2+ increase in submembraneous signaling compartments by means of ER tethering.

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“…In addition, in vivo experiments showed that overexpression of CLCA1 could inhibit the proliferation and metastasis of colon cancer [31]. It has been proved that CLCA1 is closely related to TMEM16A, and CLCA1 can regulate TMEM16A to participate in the proliferation, migration and invasion of colorectal cancer cells [32][33][34]. It is well known that c-myc is a pro-oncogene and its products closely regulate cell proliferation and apoptosis.…”

Section: Discussionmentioning

confidence: 99%

CLCA1 Has a Prognostic Indicator for the Colorectal Cancer by Weighted Gene Co-Expression Network Analysis

lin¹,

Yang²,

Lin³

et al. 2021

Preprint

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Colorectal cancer (CRC) has become the second most common digestive tract tumor. Even though the means to treat colon cancer have improved, patients prognosis is low due to the lack of accurate molecular targets. Hence, it urgently demanded better biomarkers for prognosis and progression of colon cancer. This study explores the hub gene associated with the prognosis of colorectal cancer and further analyzes the hub gene function. In this study, all genes mRNA expression data were from the cancer genome atlas (TCGA) colon cancer database and the Gene Expression Omnibus (GEO). These databases were used to screen the differentially expressed co-genes between colon cancer tissue and normal tissue. Weighted Gene Co-expression Network Analysis screened out a total of 103 differential co-expression genes (WGCNA). According to the R cluster profile package annotation analysis, these genes biological functions mainly concentrate on energy metabolism. Moreover, in the protein-protein interaction (PPI) network, the CytoHubba plugin of Cytoscape was used to screen out ten genes (CLCA1, ZG16, GUCA2B, GUCA2A, CLCA4, SLC26A3, MS4A12, GCG, SI, and NR1H4). According to the survival analysis results, high expression of CLCA1has better overall survival and disease-free survival in patients with CRC. Simultaneously, the mRNA expression of CLCA1 in normal tissues was higher than that in CRC tissues. Besides, there were significant differences in the expression of CLCA1 in pathological stage, T stage, and M stage. By using a gene set enrichment analysis, we found several considerable enrichment pathways in the high-groups. CIBERSORT analysis for the proportion of TICs revealed that B-cell naive, dendritic cells, plasma cells, and CD4+ T cells were positively correlated with CLCA1 expression, suggesting that CLCA1 might be responsible for the preservation of immune-dominant status for TME. Finally, in the Human Protein Atlas (HPA) database, the protein level of CLCA1 in the colorectal cancer samples decreased, consistent with the down-regulation of the mRNA expression level CLCA1. To sum up, by integrating WGCNA with differential gene expression analysis, this research generated a significant survival correlative gene called CLCA1 that can predict prognosis prediction in colon cancer.

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Calcium-Activated Cl− Channel: Insights on the Molecular Identity in Epithelial Tissues

Cited by 10 publications

References 76 publications

Korean Red Ginseng aqueous extract improves markers of mucociliary clearance by stimulating chloride secretion

Korean Red Ginseng aqueous extract improves markers of mucociliary clearance by stimulating chloride secretion

Ca2+ Dependence of Volume-Regulated VRAC/LRRC8 and TMEM16A Cl– Channels

CLCA1 Has a Prognostic Indicator for the Colorectal Cancer by Weighted Gene Co-Expression Network Analysis

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