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  • American Physiological Society  (14)
  • 1
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    Online Resource
    Divergent changes of p53 in pulmonary arterial endothelial and smooth muscle cells involved in the development of pulmonary hypertension
    American Physiological Society ; 2019
    In:  American Journal of Physiology-Lung Cellular and Molecular Physiology Vol. 316, No. 1 ( 2019-01-01), p. L216-L228
    Details
    In: American Journal of Physiology-Lung Cellular and Molecular Physiology, American Physiological Society, Vol. 316, No. 1 ( 2019-01-01), p. L216-L228
    Abstract: The tumor-suppressive role of p53, a transcription factor that regulates the expression of many genes, has been linked to cell cycle arrest, apoptosis, and senescence. The noncanonical function or the pathogenic role of p53 has more recently been implicated in pulmonary vascular disease. We previously reported that rapid nuclear accumulation of hypoxia-inducible factor (HIF)-1α in pulmonary arterial smooth muscle cells (PASMCs) upregulates transient receptor potential channels and enhances Ca 2+ entry to increase cytosolic Ca 2+ concentration ([Ca 2+ ] cyt ). Also, we observed differences in HIF-1α/2α expression in PASMCs and pulmonary arterial endothelial cells (PAECs). Here we report that p53 is increased in PAECs, but decreased in PASMCs, isolated from mice with hypoxia-induced pulmonary hypertension (PH) and rats with monocrotaline (MCT)-induced PH (MCT-PH). The increased p53 in PAECs from rats with MCT-PH is associated with an increased ratio of Bax/Bcl-2, while the decreased p53 in PASMCs is associated with an increased HIF-1α. Furthermore, p53 is downregulated in PASMCs isolated from patients with idiopathic pulmonary arterial hypertension compared with PASMCs from normal subjects. Overexpression of p53 in normal PASMCs inhibits store-operated Ca 2+ entry (SOCE) induced by passive depletion of intracellularly stored Ca 2+ in the sarcoplasmic reticulum, while downregulation of p53 enhances SOCE. These data indicate that differentially regulated expression of p53 and HIF-1α/2α in PASMCs and PAECs and the cross talk between p53 and HIF-1α/2α in PASMCs and PAECs may play an important role in the development of PH via, at least in part, induction of PAEC apoptosis and PASMC proliferation.
    Type of Medium: Online Resource
    ISSN: 1040-0605 , 1522-1504
    URL: Article
    DOI: 10.1152/ajplung.00538.2017
    Language: English
    Publisher: American Physiological Society
    Publication Date: 2019
    detail.hit.zdb_id: 1477300-4
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  • 2
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    Tanshinone IIA inhibits lipopolysaccharide-induced MUC1 overexpression in alveolar epithelial cells
    American Physiological Society ; 2014
    In:  American Journal of Physiology-Cell Physiology Vol. 306, No. 1 ( 2014-01-01), p. C59-C65
    Details
    In: American Journal of Physiology-Cell Physiology, American Physiological Society, Vol. 306, No. 1 ( 2014-01-01), p. C59-C65
    Abstract: The anti-inflammatory function of tanshinone IIA (TIIA), an active natural compound from Chinese herbal medicine Danshen, has been well recognized, and therefore TIIA has been widely used to treat various inflammatory conditions associated with cardiac and lung diseases. Mucin 1 (Muc1) plays important anti-inflammatory roles in resolution of acute lung inflammation. In this study, we investigated the effects of TIIA on LPS-induced acute lung inflammation, as well as its relationship to Muc1 expression in mouse lung and MUC1 in human alveolar epithelial cells. TIIA pretreatment significantly inhibited LPS-induced pulmonary inflammation in both Muc1 wild-type ( Muc1 +/+ ) and knockout ( Muc1 −/− ) mice, as manifested by reduced neutrophil infiltration and reduced TNF-α and keratinocyte chemoattractant levels in bronchoalveolar lavage fluid. The inhibitory effects of TIIA on airway inflammation were associated with reduced expression of Muc1 in Muc1 +/+ mouse lung. Moreover, pretreatment with TIIA significantly inhibited LPS-induced MUC1 expression and TNF-α release in A549 alveolar epithelial cells. TNF-α upregulated MUC1 mRNA and protein expression in A549 cells, which was inhibited by pretreatment with TIIA. The LPS-induced MUC1 expression was blocked when A549 cells were transfected with siRNA targeting for TNF-α receptor 1. Furthermore, TIIA inhibited LPS-induced nuclear translocation of NF-κB and upregulation of Toll-like receptor 4 in A549 cells. Taken together, these results demonstrate that TIIA suppressed LPS-induced acute lung inflammation regardless of the presence of Muc1, and TIIA inhibited LPS- and TNF-α-induced MUC1/Muc1 expression in airway epithelial cells, suggesting that MUC1/Muc1 does not account for the mechanisms of the anti-inflammatory effects of TIIA in the airway.
    Type of Medium: Online Resource
    ISSN: 0363-6143 , 1522-1563
    URL: Article
    DOI: 10.1152/ajpcell.00070.2013
    Language: English
    Publisher: American Physiological Society
    Publication Date: 2014
    detail.hit.zdb_id: 1477334-X
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  • 3
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    Bortezomib alleviates experimental pulmonary hypertension by regulating intracellular calcium homeostasis in PASMCs
    American Physiological Society ; 2016
    In:  American Journal of Physiology-Cell Physiology Vol. 311, No. 3 ( 2016-09-01), p. C482-C497
    Details
    In: American Journal of Physiology-Cell Physiology, American Physiological Society, Vol. 311, No. 3 ( 2016-09-01), p. C482-C497
    Abstract: The ubiquitin-proteasome system is considered to be the key regulator of protein degradation. Bortezomib (BTZ) is the first proteasome inhibitor approved by the US Food and Drug Administration for treatment of relapsed multiple myeloma and mantle cell lymphoma. Recently, BTZ treatment was reported to inhibit right ventricular hypertrophy and vascular remodeling in hypoxia-exposed and monocrotaline-injected rats. However, the underlying mechanisms remain poorly understood. We previously confirmed that hypoxia-elevated basal intracellular Ca 2+ concentration ([Ca 2+ ] i ) and store-operated Ca 2+ entry (SOCE) in pulmonary artery smooth muscle cells (PASMCs) are involved in pulmonary vascular remodeling. In this study we aim to determine whether BTZ attenuates the hypoxia-induced elevation of [Ca 2+ ] in PASMCs and the signaling pathway involved in this mechanism. Our results showed that 1) in hypoxia- and monocrotaline-induced rat pulmonary hypertension (PH) models, BTZ markedly attenuated the development and progression of PH, 2) BTZ inhibited the hypoxia-induced increase in cell proliferation, basal [Ca 2+ ] i , and SOCE in PASMCs, and 3) BTZ significantly normalized the hypoxia-upregulated expression of hypoxia-inducible factor-1α, bone morphogenetic protein 4, canonical transient receptor potential isoforms 1 and 6, and the hypoxia-downregulated expression of peroxisome proliferator-activated receptor-γ in rat distal pulmonary arteries and PASMCs. These results indicate that BTZ exerts its protective role in the development of PH potentially by inhibiting the canonical transient receptor potential-SOCE-[Ca 2+ ] i signaling axis in PASMCs.
    Type of Medium: Online Resource
    ISSN: 0363-6143 , 1522-1563
    URL: Article
    DOI: 10.1152/ajpcell.00324.2015
    Language: English
    Publisher: American Physiological Society
    Publication Date: 2016
    detail.hit.zdb_id: 1477334-X
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  • 4
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    Noggin inhibits hypoxia-induced proliferation by targeting store-operated calcium entry and transient receptor potential cation channels
    American Physiological Society ; 2015
    In:  American Journal of Physiology-Cell Physiology Vol. 308, No. 11 ( 2015-06-01), p. C869-C878
    Details
    In: American Journal of Physiology-Cell Physiology, American Physiological Society, Vol. 308, No. 11 ( 2015-06-01), p. C869-C878
    Abstract: Abnormally elevated bone morphogenetic protein 4 (BMP4) expression and mediated signaling play a critical role in the pathogenesis of chronic hypoxia-induced pulmonary hypertension (CHPH). In this study, we investigated the expression level and functional significance of four reported naturally occurring BMP4 antagonists, noggin, follistatin, gremlin1, and matrix gla protein (MGP), in the lung and distal pulmonary arterial smooth muscle cell (PASMC). A 21-day chronic hypoxic (10% O 2 ) exposure rat model was utilized, which has been previously shown to successfully establish experimental CHPH. Among the four antagonists, noggin, but not the other three, was selectively downregulated by hypoxic exposure in both the lung tissue and PASMC, in correlation with markedly elevated BMP4 expression, suggesting that the loss of noggin might account for the hypoxia-triggered BMP4 signaling transduction. Then, by using treatment of extrogenous recombinant noggin protein, we further found that noggin significantly normalized 1) BMP4-induced phosphorylation of cellular p38 and ERK1/2; 2) BMP4-induced phosphorylation of cellular JAK2 and STAT3; 3) hypoxia-induced PASMC proliferation; 4) hypoxia-induced store-operated calcium entry (SOCE), and 5) hypoxia-increased expression of transient receptor potential cation channels (TRPC1 and TRPC6) in PASMC. In combination, these data strongly indicated that the hypoxia-suppressed noggin accounts, at least partially, for hypoxia-induced excessive PASMC proliferation, while restoration of noggin may be an effective way to inhibit cell proliferation by suppressing SOCE and TRPC expression.
    Type of Medium: Online Resource
    ISSN: 0363-6143 , 1522-1563
    URL: Article
    DOI: 10.1152/ajpcell.00349.2014
    Language: English
    Publisher: American Physiological Society
    Publication Date: 2015
    detail.hit.zdb_id: 1477334-X
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  • 5
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    Expression of store-operated Ca 2+ entry and transient receptor potential canonical and vanilloid-related proteins in rat distal pulmonary venous smooth muscle
    American Physiological Society ; 2010
    In:  American Journal of Physiology-Lung Cellular and Molecular Physiology Vol. 299, No. 5 ( 2010-11), p. L621-L630
    Details
    In: American Journal of Physiology-Lung Cellular and Molecular Physiology, American Physiological Society, Vol. 299, No. 5 ( 2010-11), p. L621-L630
    Abstract: Chronic hypoxia causes remodeling and alters contractile responses in both pulmonary arteries and pulmonary veins. Although pulmonary arteries have been studied extensively in these disorders, the mechanisms by which pulmonary veins respond to hypoxia and whether these responses contribute to chronic hypoxic pulmonary hypertension remain poorly understood. In pulmonary arterial smooth muscle, we have previously demonstrated that influx of Ca 2+ through store-operated calcium channels (SOCC) thought to be composed of transient receptor potential (TRP) proteins is likely to play an important role in development of chronic hypoxic pulmonary hypertension. To determine whether this mechanism could also be operative in pulmonary venous smooth muscle, we measured intracellular Ca 2+ concentration ([Ca 2+ ] i ) by fura-2 fluorescence microscopy in primary cultures of pulmonary venous smooth muscle cells (PVSMC) isolated from rat distal pulmonary veins. In cells perfused with Ca 2+ -free media containing cyclopiazonic acid (10 μM) and nifedipine (5 μM) to deplete sarcoplasmic reticulum Ca 2+ stores and block voltage-dependent Ca 2+ channels, restoration of extracellular Ca 2+ (2.5 mM) caused marked increases in [Ca 2+ ] i , whereas MnCl 2 (200 μM) quenched fura-2 fluorescence, indicating store-operated Ca 2+ entry (SOCE). SKF-96365 and NiCl 2 , antagonists of SOCC, blocked SOCE at concentrations that did not alter Ca 2+ responses to 60 mM KCl. Of the seven known canonical TRP (TRPC1–7) and six vanilloid-related TRP channels (TRPV1–6), real-time PCR revealed mRNA expression of TRPC1 〉 TRPC6 〉 TRPC4 〉 TRPC2 ≈ TRPC5 〉 TRPC3, TRPV2 〉 TRPV4 〉 TRPV1 in distal PVSMC, and TRPC1 〉 TRPC6 〉 TRPC3 〉 TRPC4 ≈ TRPC5, TRPV2 ≈ TRPV4 〉 TRPV1 in rat distal pulmonary vein (PV) smooth muscle. Western blotting confirmed protein expression of TRPC1, TRPC6, TRPV2, and TRPV4 in both PVSMC and PV. Our results suggest that SOCE through Ca 2+ channels composed of TRP proteins may contribute to Ca 2+ signaling in rat distal PV smooth muscle.
    Type of Medium: Online Resource
    ISSN: 1040-0605 , 1522-1504
    URL: Article
    DOI: 10.1152/ajplung.00176.2009
    Language: English
    Publisher: American Physiological Society
    Publication Date: 2010
    detail.hit.zdb_id: 1477300-4
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  • 6
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    Sildenafil inhibits chronically hypoxic upregulation of canonical transient receptor potential expression in rat pulmonary arterial smooth muscle
    American Physiological Society ; 2010
    In:  American Journal of Physiology-Cell Physiology Vol. 298, No. 1 ( 2010-01), p. C114-C123
    Details
    In: American Journal of Physiology-Cell Physiology, American Physiological Society, Vol. 298, No. 1 ( 2010-01), p. C114-C123
    Abstract: In pulmonary arterial smooth muscle cells (PASMCs), Ca 2+ influx through store-operated Ca 2+ channels thought to be composed of canonical transient receptor potential (TRPC) proteins is an important determinant of intracellular free calcium concentration ([Ca 2+ ] i ) and pulmonary vascular tone. Sildenafil, a type V phosphodiesterase inhibitor that increases cellular cGMP, is recently identified as a promising agent for treatment of pulmonary hypertension. We previously demonstrated that chronic hypoxia elevated basal [Ca 2+ ] i in PASMCs due in large part to enhanced store-operated Ca 2+ entry (SOCE); moreover, ex vivo exposure to prolonged hypoxia (4% O 2 for 60 h) upregulated TRPC1 and TRPC6 expression in PASMCs. We examined the effect of sildenafil on basal [Ca 2+ ] i , SOCE, and the expression of TRPC in PASMCs under prolonged hypoxia exposure. We also examined the effect of sildenafil on TRPC1 and TRPC6 expression in pulmonary arterial smooth muscle (PA) from rats that developed chronically hypoxic pulmonary hypertension (CHPH). Compared with vehicle control, treatment with sildenafil (300 nM) inhibited prolonged hypoxia induced increases of 1) basal [Ca 2+ ] i , 2) SOCE, and 3) mRNA and protein expression of TRPC in PASMCs. Moreover, sildenafil (50 mg · kg −1 · day −1 ) inhibited mRNA and protein expression of TRPC1 and TRPC6 in PA from chronically hypoxic (10% O 2 for 21 days) rats, which was associated with decreased right ventricular pressure and right ventricular hypertrophy. Furthermore, we found, in PASMCs exposed to prolonged hypoxia, that knockdown of TRPC1 or TRPC6 by their specific small interference RNA attenuated the hypoxic increases of SOCE and basal [Ca 2+ ] i , suggesting a cause and effect link between increases of TRPC1 and TRPC6 expression and the hypoxic increases of SOCE and basal [Ca 2+ ] i . These results suggest that sildenafil may alter basal [Ca 2+ ] i in PASMCs by decreasing SOCE through downregulation of TRPC1 and TRPC6 expression, thereby contributing to decreased vascular tone of pulmonary arteries during the development of CHPH.
    Type of Medium: Online Resource
    ISSN: 0363-6143 , 1522-1563
    URL: Article
    DOI: 10.1152/ajpcell.00629.2008
    Language: English
    Publisher: American Physiological Society
    Publication Date: 2010
    detail.hit.zdb_id: 1477334-X
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  • 7
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    Bone morphogenetic protein 4 enhances canonical transient receptor potential expression, store-operated Ca 2+ entry, and basal [Ca 2+ ] i in rat distal pulmonary arterial smooth muscle cells
    American Physiological Society ; 2010
    In:  American Journal of Physiology-Cell Physiology Vol. 299, No. 6 ( 2010-12), p. C1370-C1378
    Details
    In: American Journal of Physiology-Cell Physiology, American Physiological Society, Vol. 299, No. 6 ( 2010-12), p. C1370-C1378
    Abstract: Recent advances have identified an important role of bone morphogenetic protein 4 (BMP4) in pulmonary vascular remodeling, yet the underlying mechanisms remain largely unexplored. We have previously found that Ca 2+ influx through store-operated calcium channels (SOCC), which are mainly thought to be composed of canonical transient receptor potential (TRPC) proteins, likely contribute to the pathogenic development of chronic hypoxic pulmonary hypertension. In this study, we investigated the effect of BMP4 on expression of TRPC and store-operated Ca 2+ entry (SOCE) in pulmonary arterial smooth muscle cells (PASMCs). Real-time quantitative PCR and Western blotting revealed that treatment with BMP4 (50 ng/ml, 60 h) increased TRPC1, TRPC4, and TRPC6 mRNA and protein expression in growth-arrested rat distal PASMCs. Moreover, in comparison to vehicle control, cells treated with BMP4 also exhibited enhanced SOCE, and elevated basal intracellular calcium concentration ([Ca 2+ ] i ) as determined by fluorescent microscopy using the Ca 2+ indicator Fura-2 AM. Perfusing cells with Ca 2+ -free Krebs-Ringer bicarbonate solution (KRBS) or KRBS containing SOCC antagonists SKF-96365 or NiCl 2 attenuated the increases in basal [Ca 2+ ] i caused by BMP4. Specific knockdown of BMP4 by small interference RNA significantly decreased the mRNA and protein expression of TRPC1, TRPC4, and TRPC6 and reduced SOCE and basal [Ca 2+ ] i in serum-stimulated PASMCs. We conclude that BMP4 regulates calcium signaling in PASMCs likely via upregulation of TRPC expression, leading to enhanced SOCE and basal [Ca 2+ ] i in PASMCs, and by this mechanism contributes to pulmonary vascular remodeling during pulmonary arterial hypertension.
    Type of Medium: Online Resource
    ISSN: 0363-6143 , 1522-1563
    URL: Article
    DOI: 10.1152/ajpcell.00040.2010
    Language: English
    Publisher: American Physiological Society
    Publication Date: 2010
    detail.hit.zdb_id: 1477334-X
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  • 8
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    Sodium tanshinone IIA sulfonate inhibits hypoxia-induced enhancement of SOCE in pulmonary arterial smooth muscle cells via the PKG-PPAR-γ signaling axis
    American Physiological Society ; 2016
    In:  American Journal of Physiology-Cell Physiology Vol. 311, No. 1 ( 2016-07-01), p. C136-C149
    Details
    In: American Journal of Physiology-Cell Physiology, American Physiological Society, Vol. 311, No. 1 ( 2016-07-01), p. C136-C149
    Abstract: Our laboratory previously showed that sodium tanshinone IIA sulfonate (STS) inhibited store-operated Ca 2+ entry (SOCE) through store-operated Ca 2+ channels (SOCC) via downregulating the expression of transient receptor potential canonical proteins (TRPC), which contribute to the formation of SOCC (Wang J, Jiang Q, Wan L, Yang K, Zhang Y, Chen Y, Wang E, Lai N, Zhao L, Jiang H, Sun Y, Zhong N, Ran P, Lu W. Am J Respir Cell Mol Biol 48: 125–134, 2013). The detailed molecular mechanisms by which STS inhibits SOCE and downregulates TRPC, however, remain largely unknown. We have previously shown that, under hypoxic conditions, inhibition of protein kinase G (PKG) and peroxisome proliferator-activated receptor-γ (PPAR-γ) signaling axis results in the upregulation of TRPC (Wang J, Yang K, Xu L, Zhang Y, Lai N, Jiang H, Zhang Y, Zhong N, Ran P, Lu W. Am J Respir Cell Mol Biol 49: 231–240, 2013). This suggests that strategies targeting the restoration of this signaling pathway may be an effective treatment strategy for pulmonary hypertension. In this study, our results demonstrated that STS treatment can effectively prevent the hypoxia-mediated inhibition of the PKG-PPAR-γ signaling axis in rat distal pulmonary arterial smooth muscle cells (PASMCs) and distal pulmonary arteries. These effects of STS treatment were blocked by pharmacological inhibition or specific small interfering RNA knockdown of either PKG or PPAR-γ. Moreover, targeted PPAR-γ agonist markedly enhanced the beneficial effects of STS. These results comprehensively suggest that STS treatment can prevent hypoxia-mediated increases in intracellular calcium homeostasis and cell proliferation, by targeting and restoring the hypoxia-inhibited PKG-PPAR-γ signaling pathway in PASMCs.
    Type of Medium: Online Resource
    ISSN: 0363-6143 , 1522-1563
    URL: Article
    DOI: 10.1152/ajpcell.00252.2015
    Language: English
    Publisher: American Physiological Society
    Publication Date: 2016
    detail.hit.zdb_id: 1477334-X
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  • 9
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    Bone morphogenetic protein 2 decreases TRPC expression, store-operated Ca 2+ entry, and basal [Ca 2+ ] i in rat distal pulmonary arterial smooth muscle cells
    American Physiological Society ; 2013
    In:  American Journal of Physiology-Cell Physiology Vol. 304, No. 9 ( 2013-05-01), p. C833-C843
    Details
    In: American Journal of Physiology-Cell Physiology, American Physiological Society, Vol. 304, No. 9 ( 2013-05-01), p. C833-C843
    Abstract: Recent studies indicate that multiple bone morphogenetic protein (BMP) family ligands and receptors are involved in the development of pulmonary arterial hypertension, yet the underlying mechanisms are incompletely understood. Although BMP2 and BMP4 share high homology in amino acid sequence, they appear to exert divergent effects on chronic hypoxic pulmonary hypertension (CHPH). While BMP4 promotes vascular remodeling, BMP2 prevents CHPH. We previously demonstrated that BMP4 upregulates the expression of canonical transient receptor potential channel (TRPC) proteins and, thereby, enhances store-operated Ca 2+ entry (SOCE) and elevates intracellular Ca 2+ concentration ([Ca 2+ ] i ) in pulmonary arterial smooth muscle cells (PASMCs). In this study, we investigated the effects of BMP2 on these variables in rat distal PASMCs. We found that treatment with BMP2 (50 ng/ml, 60 h) inhibited TRPC1, TRPC4, and TRPC6 mRNA and protein expression. Moreover, BMP2 treatment led to reduced SOCE and decreased basal [Ca 2+ ] i in PASMCs. These alterations were associated with decreased PASMC proliferation and migration. Conversely, knockdown of BMP2 with specific small interference RNA resulted in increased cellular levels of TRPC1, TRPC4, and TRPC6 mRNA and protein, enhanced SOCE, elevated basal [Ca 2+ ] i , and increased proliferation and migration of PASMCs. Together, these results indicate that BMP2 participates in regulating Ca 2+ signaling in PASMCs by inhibiting TRPC1, TRPC4, and TRPC6 expression, thus leading to reduced SOCE and basal [Ca 2+ ] i and inhibition of cell proliferation and migration.
    Type of Medium: Online Resource
    ISSN: 0363-6143 , 1522-1563
    URL: Article
    DOI: 10.1152/ajpcell.00036.2012
    Language: English
    Publisher: American Physiological Society
    Publication Date: 2013
    detail.hit.zdb_id: 1477334-X
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  • 10
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    Effects of chronic exposure to cigarette smoke on canonical transient receptor potential expression in rat pulmonary arterial smooth muscle
    American Physiological Society ; 2014
    In:  American Journal of Physiology-Cell Physiology Vol. 306, No. 4 ( 2014-02-15), p. C364-C373
    Details
    In: American Journal of Physiology-Cell Physiology, American Physiological Society, Vol. 306, No. 4 ( 2014-02-15), p. C364-C373
    Abstract: To clarify the possible mechanism of cigarette smoke (CS)-induced pulmonary hypertension and furthermore provide effective targets for prevention and treatment, the effects of chronic CS on rat pulmonary arterial smooth muscle in vivo and nicotine treatment on rat pulmonary arterial smooth muscle cells (PASMCs) in vitro were investigated. In this study, we demonstrated that chronic CS exposure led to rat weight loss, right ventricular hypertrophy, and pulmonary arterial remodeling. A fluorescence microscope was used to measure intracellular calcium concentration ([Ca 2+ ] i ) in rat distal PASMCs. Results showed that basal [Ca 2+ ] i and store-operated calcium entry (SOCE) levels in PASMCs from 3- and 6-mo CS-exposed rats were markedly higher than those in cells from the unexposed control animals (the increases in 6-mo CS group were more significant than that in 3-mo group), accompanied with increased canonical transient receptor potential 1 (TRPC1) and TRPC6 expression at both mRNA and protein levels in isolated distal PA. Simultaneously, in vitro study showed that nicotine treatment (10 nM) significantly increased basal [Ca 2+ ] i and SOCE and upregulated TRPC1 and TRPC6 expression in cultured rat distal PASMCs. TRPC siRNA knockdown strategies revealed that the elevations of basal [Ca 2+ ] i and SOCE induced by nicotine in PASMCs were TRPC1 and TRPC6 dependent. These results suggested that chronic CS-induced changes in vascular tone and structure in PA and the development of pulmonary hypertension might be largely due to upregulation of TRPC1 and TRPC6 expression in PASMCs, in which nicotine played an important role.
    Type of Medium: Online Resource
    ISSN: 0363-6143 , 1522-1563
    URL: Article
    DOI: 10.1152/ajpcell.00048.2013
    Language: English
    Publisher: American Physiological Society
    Publication Date: 2014
    detail.hit.zdb_id: 1477334-X
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