Canonical Transient Potential Receptor-3 Channels in Normal and Diseased Airway Smooth Muscle Cells

Wang, Yong-Xiao; Wang, Lan; Zheng, Yun‐Min

doi:10.1007/978-3-030-12457-1_18

Cited by 5 publications

(4 citation statements)

References 84 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We have previously shown that human fASM expresses IP3R (Hartman et al, ) and results from our current study with U73122 (PLC inhibitor), PLCβ siRNA, and XeC (IP 3 R blocker) underline the link between CaSR and the PLC‐IP 3 pathway in developing ASM. The expression and role of TRPC channels in adult ASM has also been previously demonstrated (Prakash, ; Wang & Zheng, ) and we have previously reported expression of TRPC channels (Hartman et al, ) in human fASM cells. Thus, our data showing enhancement of SOCE by CaSR suggests a link between CaSR and TRPCs in fASM.…”

Section: Discussionsupporting

confidence: 79%

Calcium sensing receptor in developing human airway smooth muscle

Roesler

Wicher

Ravix

et al. 2019

Journal Cellular Physiology

View full text Add to dashboard Cite

Airway smooth muscle (ASM) regulation of airway structure and contractility is critical in fetal/neonatal physiology in health and disease. Fetal lungs experience higher Ca2+ environment that may impact extracellular Ca2+ ([Ca2+]o) sensing receptor (CaSR). Well‐known in the parathyroid gland, CaSR is also expressed in late embryonic lung mesenchyme. Using cells from 18‐22 week human fetal lungs, we tested the hypothesis that CaSR regulates intracellular Ca2+ ([Ca2+]i) in fetal ASM (fASM). Compared with adult ASM, CaSR expression was higher in fASM, while fluorescence Ca2+ imaging showed that [Ca2+]i was more sensitive to altered [Ca2+]o. The fASM [Ca2+]i responses to histamine were also more sensitive to [Ca2+]o (0–2 mM) compared with an adult, enhanced by calcimimetic R568 but blunted by calcilytic NPS2143. [Ca2+]i was enhanced by endogenous CaSR agonist spermine (again higher sensitivity compared with adult). Inhibition of phospholipase C (U73122; siRNA) or inositol 1,4,5‐triphosphate receptor (Xestospongin C) blunted [Ca2+]o sensitivity and R568 effects. NPS2143 potentiated U73122 effects. Store‐operated Ca2+ entry was potentiated by R568. Traction force microscopy showed responsiveness of fASM cellular contractility to [Ca2+]o and NPS2143. Separately, fASM proliferation showed sensitivity to [Ca2+]o and NPS2143. These results demonstrate functional CaSR in developing ASM that modulates airway contractility and proliferation.

show abstract

Section: Discussionsupporting

confidence: 79%

Calcium sensing receptor in developing human airway smooth muscle

Roesler

Wicher

Ravix

et al. 2019

Journal Cellular Physiology

View full text Add to dashboard Cite

show abstract

“…Calcium (Ca 2+ ) signaling is a key regulator of numerous short-term and long-term cellular functions including contraction and activation of transcriptional programs that control proliferation, migration, secretion, and metabolism ( 13 ). Smooth muscle phenotypic switch is characterized by extensive remodeling of the cellular ion channel repertoire with major changes in expression and regulation of Ca 2+ channels and transporters ( 14 – 21 ).The store-operated Ca 2+ entry (SOCE) pathway has emerged as particularly critical for vascular smooth muscle and cardiomyocyte remodeling during cardiovascular disease ( 22 , 23 ). SOCE is activated by the binding of agonists, growth factors, and inflammatory mediators to receptors coupled to phospholipase-C (PLC) isoforms.…”

mentioning

confidence: 99%

STIM1 is a core trigger of airway smooth muscle remodeling and hyperresponsiveness in asthma

Johnson

Xin

Benson

et al. 2021

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Airway remodeling and airway hyperresponsiveness are central drivers of asthma severity. Airway remodeling is a structural change involving the dedifferentiation of airway smooth muscle (ASM) cells from a quiescent to a proliferative and secretory phenotype. Here, we show up-regulation of the endoplasmic reticulum Ca2+ sensor stromal-interacting molecule 1 (STIM1) in ASM of asthmatic mice. STIM1 is required for metabolic and transcriptional reprogramming that supports airway remodeling, including ASM proliferation, migration, secretion of cytokines and extracellular matrix, enhanced mitochondrial mass, and increased oxidative phosphorylation and glycolytic flux. Mechanistically, STIM1-mediated Ca2+ influx is critical for the activation of nuclear factor of activated T cells 4 and subsequent interleukin-6 secretion and transcription of pro-remodeling transcription factors, growth factors, surface receptors, and asthma-associated proteins. STIM1 drives airway hyperresponsiveness in asthmatic mice through enhanced frequency and amplitude of ASM cytosolic Ca2+ oscillations. Our data advocates for ASM STIM1 as a target for asthma therapy.

show abstract

“…Oxidative stress and inflammation can lead to increased expression of NF‐κBiz and induce a variety of downstream molecules to participate in defense response 37 . TRPC3‐mediated increase in Ca 2+ signaling activates the transcription factor NF‐κB via the IκB, causing cell proliferation and leading to airway remodeling 38 . Therefore, in this study, we hypothesized that TRPC3 might be involved in the pathogenesis of BPD through the NF‐κB signaling pathway.…”

Section: Discussionmentioning

confidence: 94%

“…37 TRPC3mediated increase in Ca 2þ signaling activates the transcription factor NF-κB via the IκB, causing cell proliferation and leading to airway remodeling. 38 Therefore, in this study, we hypothesized that TRPC3 might be involved in the pathogenesis of BPD through the NF-κB signaling pathway. According to our results, under the condition of hyperoxia, the expression of TRPC3 in the BPD model decreases, the expression of NF-κBiz increases, and the expression and activity of NF-κB are reduced, which may inhibit cell proliferation and cause lung growth arrest.…”

Section: Discussionmentioning

confidence: 95%

Effect and mechanism of transient receptor potential canonical channel 3 on hyperoxic lung injury in neonatal rats

Fu,

Gong,

et al. 2024

Pediatric Discovery

View full text Add to dashboard Cite

The aim of this study is to research the expression of the transient receptor potential canonical channel 3 (TRPC3) in a neonatal hyperoxic lung injury model of bronchopulmonary dysplasia (BPD), and to further investigate the role of the TRPC3/nuclear factor‐κB (NF‐κB) signaling pathway in hyperoxia‐induced BPD by a TRPC3 agonist (GSK1702934A). The hyperoxic lung injury model of BPD was established in Sprague–Dawley neonatal rats. Hematoxylin and eosin (HE) staining and radial alveolar count (RAC) values showed that the hyperoxic lung injury model of BPD was successfully established in the neonatal rats, and pulmonary edema was found in the neonatal rats with BPD. The results of reference transcriptome sequencing, Quantitative real‐time PCR (qPCR), and western blot showed lower pulmonary expression of TRPC3 in the BPD group than in the control group. Immunofluorescence showed predominant expression of TRPC3 in airways and pulmonary vessels, and the fluorescence intensity of the BPD group was lower than that of the control group. Lung dry‐to‐wet weight ratio, HE staining, and RAC value showed that the lung histomorphology significantly improved in the BPD + TRPC3 agonist group compared with the BPD group on day 14 but did not revert to the level of the control group. According to qPCR results, compared with the control group, the expression of NF‐κB1 decreased and the expression of NF‐κBiz increased in the BPD group, whereas the expression of NF‐κBiz decreased in the BPD + TRPC3 agonist group. Therefore, we draw the conclusion that TRPC3 may activate NF‐κB by inhibiting NF‐κBiz to promote cell proliferation and lung growth and development.

show abstract

Canonical Transient Potential Receptor-3 Channels in Normal and Diseased Airway Smooth Muscle Cells

Cited by 5 publications

References 84 publications

Calcium sensing receptor in developing human airway smooth muscle

Calcium sensing receptor in developing human airway smooth muscle

STIM1 is a core trigger of airway smooth muscle remodeling and hyperresponsiveness in asthma

Effect and mechanism of transient receptor potential canonical channel 3 on hyperoxic lung injury in neonatal rats

Contact Info

Product

Resources

About