Mechanotransduction via TRPV4 regulates inflammation and differentiation in fetal mouse distal lung epithelial cells

Nayak, Pritha S.; Wang, Yulian; Najrana, Tanbir; Priolo, Lauren; Rios, Mayra; Shaw, Sunil K.; Sanchez‐Esteban, Juan

doi:10.1186/s12931-015-0224-4

Cited by 34 publications

(26 citation statements)

References 54 publications

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“…TRPV4 is expressed in adult lung [10,11,12]; however, whether undifferentiated distal epithelial cells express TRPV4 and the response to mechanical injury were unknown. Recent studies from our laboratory have found that TRPV4 is expressed in the fetal lung, and specifically in the bronchial and distal epithelium [13]. Moreover, in vitro experiments in isolated distal epithelial cells found that TRPV4 expression level responded to mechanical signals.…”

Section: +mentioning

confidence: 87%

“…Moreover, in vitro experiments in isolated distal epithelial cells found that TRPV4 expression level responded to mechanical signals. This response was gestational-age dependent, being the canalicular stage of lung development the period of gestation more sensitive to mechanical injury [13].…”

Section: +mentioning

confidence: 99%

“…One possibility is that TRPV4 inhibitors act primarily on endothelial and epithelial cells, not only preventing changes in barrier function, but also blocking other Ca2+ dependent processes, such as the release of cytokines and adhesion molecules or the facilitation of neutrophil transit [18]. Studies from our laboratory found that TRPV4 regulates release of the pro-Inflammatory cytokine IL-6 in fetal epithelial cells exposed to injurious stretch [13]. Therefore, these investigations provide novel observations that distal fetal epithelial cells are an important source of Inflammatory cytokines, as previously shown in differentiated alveolar type II epithelial cells [19].…”

Section: +mentioning

confidence: 99%

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TRPV4 Channels: Potential Targets to Reduce the Incidence of Bronchopulmonary Dysplasia (BPD)?

Sanchez‐Esteban¹,

Najrana²

2016

IJPCC

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Section: +mentioning

confidence: 87%

Section: +mentioning

confidence: 99%

Section: +mentioning

confidence: 99%

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TRPV4 Channels: Potential Targets to Reduce the Incidence of Bronchopulmonary Dysplasia (BPD)?

Sanchez‐Esteban¹,

Najrana²

2016

IJPCC

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“…This produces a range of IL-6 change that not only changes continuously from the activation of the TRPM8 receptor at 8°C but also continues in a downward trend until the peak activity of TRPV4. 1,3 Additionally, this corresponds roughly to the range of Clostridium perfringens germination activity, which peaks roughly around 44°C in a growth curve. 4 Clostridium perfringens is a bacteria known for cold related conditions such as gangrene.…”

Section: Introductionmentioning

confidence: 96%

A model for the identification of polymorphisms responsible for common genetic conditions and its relationship to multiple sclerosis

Heisten¹

2018

Pol Ann Med

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I n t r o d u c t i o n : Analy�ing whether genetic polymorphisms proven responsi-Analy�ing whether genetic polymorphisms proven responsible for known genetic conditions are equal in incidence to the prevalence of those conditions may demonstrate a means to identify polymorphisms responsible for genetic conditions without a known genetic basis. Performing the same analysis on the temperature sensing region of the TRPM8 receptor in relation to multiple sclerosis (MS) could provide evidence of a genetic basis for MS in the TRPM8 receptor.A i m : To test if correlation between the incidence of a genetic polymorphism and the prevalence of a genetic-linked condition in a large population can identify a polymorphism that could be associated with MS. M a t e r i a l s a n d m e t h o d s : Prevalences of genetic conditions with known genetic polymorphism responsible for that condition were matched to the genetic incidence of the polymorphism proven to cause that condition. The model was then used to identify MS candidate polymorphisms in the S4-S5 region of TRPM8. The University of California Southern California Genome Browser was used for this comparison to identify polymorphism incidence rates.Results and discussion: Two polymorphisms, Rs28902201 on exon 19 and Rs149328116 on exon 20, were identified as candidate polymorphisms for MS. Other polymorphisms at these loci can contribute to the overall prevalence of MS. Rare variants that have the same genetic effect as the predominant polymorphism responsible for a condition can affect local populations significantly.C o n c l u s i o n s : Rs28902201 and Rs149328116 are candidate variants for MS based on their incidence in the population and the similarity of these incidences to MS prevalence rates.

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“…Due to its expression in the adult lung, TRPV4 has been implicated in mediating the mechanosensitive response to ventilator-induced barotrauma 22,23 . While this response has been minimally investigated in late fetal lungs 49 , TRPV4’s direct correlation to early lung development remains unstudied.…”

Section: Introductionmentioning

confidence: 99%

The Mechanosensitive Ion Channel TRPV4 is a Regulator of Lung Development and Pulmonary Vasculature Stabilization

et al. 2018

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Introduction – Clinical observations and animal models suggest a critical role for the dynamic regulation of transmural pressure and peristaltic airway smooth muscle contractions for proper lung development. However, it is currently unclear how such mechanical signals are transduced into molecular and transcriptional changes at the cell level. To connect these physical findings to a mechanotransduction mechanism, we identified a known mechanosensor, TRPV4, as a component of this pathway. Methods – Embryonic mouse lung explants were cultured on membranes and in submersion culture to modulate explant transmural pressure. Time-lapse imaging was used to capture active changes in lung biology, and whole-mount images were used to visualize the organization of the epithelial, smooth muscle, and vascular compartments. TRPV4 activity was modulated by pharmacological agonism and inhibition. Results – TRPV4 expression is present in the murine lung with strong localization to the epithelium and major pulmonary blood vessels. TRPV4 agonism and inhibition resulted in hyper- and hypoplastic airway branching, smooth muscle differentiation, and lung growth, respectively. Smooth muscle contractions also doubled in frequency with agonism and were reduced by 60% with inhibition demonstrating a functional role consistent with levels of smooth muscle differentiation. Activation of TRPV4 increased the vascular capillary density around the distal airways, and inhibition resulted in a near complete loss of the vasculature. Conclusions – These studies have identified TRPV4 as a potential mechanosensor involved in transducing mechanical forces on the airways to molecular and transcriptional events that regulate the morphogenesis of the three essential tissue compartments in the lung.

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Mechanotransduction via TRPV4 regulates inflammation and differentiation in fetal mouse distal lung epithelial cells

Cited by 34 publications

References 54 publications

TRPV4 Channels: Potential Targets to Reduce the Incidence of Bronchopulmonary Dysplasia (BPD)?

TRPV4 Channels: Potential Targets to Reduce the Incidence of Bronchopulmonary Dysplasia (BPD)?

A model for the identification of polymorphisms responsible for common genetic conditions and its relationship to multiple sclerosis

The Mechanosensitive Ion Channel TRPV4 is a Regulator of Lung Development and Pulmonary Vasculature Stabilization

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