TRPA1 channels: expression in non-neuronal murine lung tissues and dispensability for hyperoxia-induced alveolar epithelial hyperplasia

Kannler, Martina; Lüling, Robin; Yildirim, Ali Önder; Gudermann, Thomas; Steinritz, Dirk; Dietrich, Alexander

doi:10.1007/s00424-018-2148-6

Cited by 16 publications

(10 citation statements)

References 45 publications

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“…Direct quantification of TRPV4 mRNA in murine lung cells was done as described previously ( 62 ). In brief, total RNA from pulmonary murine cells was isolated using the Qia RNeasy Mini Kit (QIAGEN).…”

Section: Methodsmentioning

confidence: 99%

TRPV4 channels are essential for alveolar epithelial barrier function as protection from lung edema

et al. 2020

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Ischemia/reperfusion-induced edema (IRE), one of the most significant causes of mortality after lung transplantation, can be mimicked ex vivo in isolated perfused mouse lungs (IPL). Transient receptor potential vanilloid 4 (TRPV4) is a nonselective cation channel studied in endothelium; however, its role in the lung epithelium remains elusive. Here, we show enhanced IRE in TRPV4-deficient (TRPV4 –/– ) IPL compared with that of WT controls, indicating a protective role of TRPV4 in maintenance of the alveolar epithelial barrier. By immunohistochemistry, mRNA profiling, and electrophysiological characterization, we detected TRPV4 in bronchial epithelium, alveolar epithelial type I (ATI), and alveolar epithelial type II (ATII) cells. Genetic ablation of TRPV4 resulted in reduced expression of the water-conducting aquaporin-5 (AQP-5) channel in ATI cells. Migration of TRPV4 –/– ATI cells was reduced, and cell barrier function was impaired. Analysis of isolated primary TRPV4 –/– ATII cells revealed a reduced expression of surfactant protein C, and the TRPV4 activator GSK1016790A induced increases in current densities only in WT ATII cells. Moreover, TRPV4 –/– lungs of adult mice developed significantly larger mean chord lengths and altered lung function compared with WT lungs. Therefore, our data illustrate essential functions of TRPV4 channels in alveolar epithelial cells and in protection from edema formation.

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Section: Methodsmentioning

confidence: 99%

TRPV4 channels are essential for alveolar epithelial barrier function as protection from lung edema

et al. 2020

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“…However, TRPA1-mediated effects via the sensory trigeminal afferentation of the upper airways also might contribute to our results in both models [70]. Besides the neuronal expression, TRPA1 is also located on epithelial, inflammatory and bronchial smooth muscle cells [6,47,48,50].…”

Section: Discussionmentioning

confidence: 74%

“…TRPA1 is also expressed on several non-neuronal cells [35], e.g., keratinocytes, macrophages and CD4+ lymphocytes [36][37][38], epidermal melanocytes, fibroblasts [39,40], urothelial and endothelial cells, as well as primary human osteoarthritic chondrocytes [41][42][43]. In the airways, TRPA1 is expressed on fibroblasts, tracheal, bronchial and alveolar epithelial cells, bronchial smooth muscle cells (SMC), as well as lymphocytes [17,[44][45][46][47][48][49][50].…”

Section: Introductionmentioning

confidence: 99%

Complex Regulatory Role of the TRPA1 Receptor in Acute and Chronic Airway Inflammation Mouse Models

Hajna

Csekő

Kemény

et al. 2020

IJMS

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The Transient Receptor Potential Ankyrin 1 (TRPA1) cation channel expressed on capsaicin-sensitive afferents, immune and endothelial cells is activated by inflammatory mediators and exogenous irritants, e.g., endotoxins, nicotine, crotonaldehyde and acrolein. We investigated its involvement in acute and chronic pulmonary inflammation using Trpa1 gene-deleted (Trpa1−/−) mice. Acute pneumonitis was evoked by intranasal Escherichia coli endotoxin (lipopolysaccharide: LPS) administration, chronic bronchitis by daily cigarette smoke exposure (CSE) for 4 months. Frequency, peak inspiratory/expiratory flows, minute ventilation determined by unrestrained whole-body plethysmography were significantly greater, while tidal volume, inspiratory/expiratory/relaxation times were smaller in Trpa1−/− mice. LPS-induced bronchial hyperreactivity, myeloperoxidase activity, frequency-decrease were significantly greater in Trpa1−/− mice. CSE significantly decreased tidal volume, minute ventilation, peak inspiratory/expiratory flows in wildtypes, but not in Trpa1−/− mice. CSE remarkably increased the mean linear intercept (histopathology), as an emphysema indicator after 2 months in wildtypes, but only after 4 months in Trpa1−/− mice. Semiquantitative histopathological scores were not different between strains in either models. TRPA1 has a complex role in basal airway function regulation and inflammatory mechanisms. It protects against LPS-induced acute pneumonitis and hyperresponsiveness, but is required for CSE-evoked emphysema and respiratory deterioration. Further research is needed to determine TRPA1 as a potential pharmacological target in the lung.

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“…Direct quantification of TRPV4 mRNA in murine lung cells was done as described ( Kannler et al, 2018 ). In brief: total RNA from pulmonary murine cells was isolated using the Qia RNeasy Mini Kit (Qiagen, Hilden, Germany).…”

Section: Methodsmentioning

confidence: 99%

Transient receptor vanilloid 4 (TRPV4) channels are essential for alveolar epithelial cell function

Weber

Chao

Kannler

et al. 2019

Preprint

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Competing interests:The authors declare that no competing interests exist. ischemia and reperfusion, indicating a protective role of TRPV4 to maintain the alveolar epithelial barrier. TRPV4 was detected in bronchial epithelium, alveolar type I (ATI) and alveolar type II (ATII) cells by immunohistochemistry or mRNA profiling. Genetic ablation of TRPV4 resulted in reduced expression and plasma membrane insertion of water conducting aquaporin-5 (AQP-5) channels in ATI cells compared to WT mice.Analysis of isolated primary TRPV4-/-ATII cells revealed a reduced expression of pro surfactant protein-C (pSP-C) a precursor of a protein important for decreasing surface tension and for alveolar fluid homeostasis. Moreover, the TRPV4 activator GSK1016790A induced increases in current densities only in WT but not in TRPV4-/-ATII cells. On a molecular level ablation of TRPV4 induced less Ca 2+ -mediated nuclear translocation of nuclear factor of activated T-cells (NFAT) to the nucleus, which may be responsible for reduced expression of the identified proteins. Although the ability of TRPV4-/-ATII to differentiate to ATI cells was unchanged, migration of TRPV4deficient ATI cells was reduced and cell barrier function was impaired. Moreover, TRPV4-/-lungs of adult mice developed significantly larger mean chord lengths and altered lung function compared to WT lungs. The findings of Weber et al. highlights novel essential functions of TRPV4 channels in alveolar epithelial cells and in the protection from edema formation. Akazawa Y, Yuki T, Yoshida H, Sugiyama Y, Inoue, S. 2013. Activation of TRPV4 strengthens the tight-junction barrier in human epidermal keratinocytes. Skin Pharmacol Physiol 26: 15-21. Alpizar YA, Boonen B, Sanchez A, Jung C, Lopez-Requena A, Naert R, Steelant B, Luyts K, Plata C, De Vooght V et al. 2017. TRPV4 activation triggers protective responses to bacterial lipopolysaccharides in airway epithelial cells. Nature communications 8: 1059. Alvarez DF, King JA, Weber D, Addison E, Liedtke W, Townsley MI 2006. Transient receptor potential vanilloid 4-mediated disruption of the alveolar septal barrier: a novel mechanism of acute lung injury. Circ Res 99: 988-995. Balakrishna S, Song W, Achanta S, Doran SF, Liu B, Kaelberer MM, Yu Z, Sui A, Cheung M, Leishman E et al. 2014. TRPV4 inhibition counteracts edema and inflammation and improves pulmonary function and oxygen saturation in chemically induced acute lung injury. American journal of physiology Lung cellular and molecular physiology 307: L158-172. Corti M, Brody AR, and Harrison JH 1996. Isolation and primary culture of murine alveolar type II cells. American journal of respiratory cell and molecular biology 14: 309-315. Curcic S, Schober R, Schindl R, Groschner K 2019. TRPC-mediated Ca(2+) signaling and control of cellular functions. Semin Cell Dev Biol. in press de Perrot M, Liu M, Waddell TK, and Keshavjee S 2003. Ischemia-reperfusion-induced lung injury. American journal of respiratory and critical care medicine 167: 490-511. Desai TJ, Brownfield DG, Krasnow ...

show abstract

TRPA1 channels: expression in non-neuronal murine lung tissues and dispensability for hyperoxia-induced alveolar epithelial hyperplasia

Cited by 16 publications

References 45 publications

TRPV4 channels are essential for alveolar epithelial barrier function as protection from lung edema

TRPV4 channels are essential for alveolar epithelial barrier function as protection from lung edema

Complex Regulatory Role of the TRPA1 Receptor in Acute and Chronic Airway Inflammation Mouse Models

Transient receptor vanilloid 4 (TRPV4) channels are essential for alveolar epithelial cell function

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