Role Of Lung Research Articles

Characterizing Canine Hepatobiliary Neuroendocrine Neoplasia: A Proteomic Approach

Hepatobiliary neuroendocrine neoplasia is an extremely rare cancer in humans and other species. In humans, neuroendocrine neoplasia of the liver and gallbladder represents less than 2% of all gastroenteropancreatic neuroendocrine neoplasia. In the veterinary literature, there is a paucity of information on hepatobiliary neuroendocrine cancer with only a small number of published studies. Improved characterization of these tumors is needed to identify additional biomarkers for diagnosis and generate informed treatment protocols for human and veterinary patients. Here, we applied a proteomics strategy to identify differentially expressed proteins in canine hepatobiliary neoplasia as compared to normal canine adrenal and liver tissue from formalin-fixed paraffin-embedded samples. Our objective was to identify unique protein biomarkers and possible chemotherapeutic targets. Thirty-four up-regulated, differentially expressed proteins were identified in the hepatobiliary neuroendocrine neoplasia samples. Galectin-1, a multivalent carbohydrate binding protein known to play a role in lung and pancreatic neuroendocrine neoplasia development and progression, was among them. Drugs targeting the galectin family have shown promise as anticancer therapeutics in cervical cancer, prostate cancer, lung and pancreatic neuroendocrine neoplasia. Galectin-1 may represent a novel treatment target in hepatobiliary neuroendocrine neoplasia in both humans and dogs.

The History and Mystery of Alveolar Epithelial Type II Cells: Focus on Their Physiologic and Pathologic Role in Lung.

Alveolar type II (ATII) cells are a key structure of the distal lung epithelium, where they exert their innate immune response and serve as progenitors of alveolar type I (ATI) cells, contributing to alveolar epithelial repair and regeneration. In the healthy lung, ATII cells coordinate the host defense mechanisms, not only generating a restrictive alveolar epithelial barrier, but also orchestrating host defense mechanisms and secreting surfactant proteins, which are important in lung protection against pathogen exposure. Moreover, surfactant proteins help to maintain homeostasis in the distal lung and reduce surface tension at the pulmonary air–liquid interface, thereby preventing atelectasis and reducing the work of breathing. ATII cells may also contribute to the fibroproliferative reaction by secreting growth factors and proinflammatory molecules after damage. Indeed, various acute and chronic diseases are associated with intensive inflammation. These include oedema, acute respiratory distress syndrome, fibrosis and numerous interstitial lung diseases, and are characterized by hyperplastic ATII cells which are considered an essential part of the epithelialization process and, consequently, wound healing. The aim of this review is that of revising the physiologic and pathologic role ATII cells play in pulmonary diseases, as, despite what has been learnt in the last few decades of research, the origin, phenotypic regulation and crosstalk of these cells still remain, in part, a mystery.

High expression of aldolase A is associated with tumor progression and poor prognosis in hepatocellular carcinoma.

Aldolase A (ALDOA), a key glycolytic enzyme, has been reported to play an important role in lung, pancreatic, and colorectal cancer. However, the role and mechanism of ALDOA in hepatocellular carcinoma (HCC) are still unclear. This study aimed to study the role and potential mechanism of ALDOA in HCC. The changes in expression level and clinical implications of ALDOA in HCC were studied through bioinformatics and online databases. The prognostic role of ALDOA was investigated by Kaplan-Meier and Cox regression survival analysis. We explored the potential mechanism of ALDOA in the development of HCC by gene set enrichment analysis (GSEA). The expression level of ALDOA was significantly increased in HCC compared with adjacent normal tissues (P<0.001). The expression level of ALDOA was significantly associated with tumor, node, metastasis (TNM) stage, histologic grade, and p53 mutation (all P<0.05). Prognostically, HCC patients with high expression of ALDOA indicated poorer prognosis and shorter survival time. In addition, univariate and multivariate Cox regression analysis further suggested that overexpression of ALDOA was an independent prognostic risk factor (P<0.05). Furthermore, the nomogram was developed based on ALDOA expression and tumor TNM stage. Besides, ALDOA DNA copy gain and methylation were associated with ALDOA upregulation in HCC. Finally, GSEA suggested that high expression of ALDOA was associated with glucose catabolic process, cell cycle, DNA replication, E2F1 pathways, protein kinase B/mammalian target of rapamycin (AKT/mTOR) pathways, and CD4 T cell related immune biological processes. There is a close relationship between ALDOA and HCC progression, and ALDOA may be a novel prognostic biomarker and a promising drug target for the treatment of HCC.

Transcriptome of nasopharyngeal samples from COVID-19 patients and a comparative analysis with other SARS-CoV-2 infection models reveal disparate host responses against SARS-CoV-2

BackgroundAlthough it is becoming evident that individual’s immune system has a decisive influence on SARS-CoV-2 disease progression, pathogenesis is largely unknown. In this study, we aimed to profile the host transcriptome of COVID-19 patients from nasopharyngeal samples along with virus genomic features isolated from respective host, and a comparative analyses of differential host responses in various SARS-CoV-2 infection systems.ResultsUnique and rare missense mutations in 3C-like protease observed in all of our reported isolates. Functional enrichment analyses exhibited that the host induced responses are mediated by innate immunity, interferon, and cytokine stimulation. Surprisingly, induction of apoptosis, phagosome, antigen presentation, hypoxia response was lacking within these patients. Upregulation of immune and cytokine signaling genes such as CCL4, TNFA, IL6, IL1A, CCL2, CXCL2, IFN, and CCR1 were observed in lungs. Lungs lacked the overexpression of ACE2 as suspected, however, high ACE2 but low DPP4 expression was observed in nasopharyngeal cells. Interestingly, directly or indirectly, viral proteins specially non-structural protein mediated overexpression of integrins such as ITGAV, ITGA6, ITGB7, ITGB3, ITGA2B, ITGA5, ITGA6, ITGA9, ITGA4, ITGAE, and ITGA8 in lungs compared to nasopharyngeal samples suggesting the possible way of enhanced invasion. Furthermore, we found comparatively highly expressed transcription factors such as CBP, CEBP, NFAT, ATF3, GATA6, HDAC2, TCF12 which have pivotal roles in lung injury.ConclusionsEven though this study incorporates a limited number of cases, our data will provide valuable insights in developing potential studies to elucidate the differential host responses on the viral pathogenesis in COVID-19, and incorporation of further data will enrich the search of an effective therapeutics.

The renin‐angiotensin system in COVID‐19: Why ACE2 targeting by coronaviruses produces higher mortality in elderly hypertensive patients?

This renin‐angiotensin system (RAS) interpretation is focused on differences in tissue dependence on RAS and on the topological hierarchy that allows mediators to act only on downstream tissues.Dependence of tissues on RAS: Tested by expectation maximization clustering of the RNA human tissue expression (https://biogps.org/). ACE and vasoconstrictive AT1R clustered with the prorenin receptor. ACE2 and dilatory MAS1 clustered with nine RAS‐related genes, highly expressed in: Liver; Cardiac_Myocytes; Skeletal_Muscle; Uterus; Kidney; Lung; Small_Intestine; Smooth_Muscle.RAS and stress accumulation: While prorenin is active after binding to its receptor, binding of soluble renin increases its enzymatic activity several times. Increased renin secretion multiplies the overall capacity for producing Ang I, leading to hypertension and increased vascular resistance.Coronavirus infection and comorbidities: Cardiorespiratory failure during infection is linked to the previously altered RAS role in lungs and myocardium. Reduced vasodilation by ACE2 lead to vasoconstriction and suboptimal tissue perfusion patterns. Also see the video abstract here https://www.youtube.com/watch?v=Jf0Iped-Mws

Imperfect storm: is interleukin-33 the Achilles heel of COVID-19?

The unique cytokine signature of COVID-19 might provide clues to disease mechanisms and possible future therapies. Here, we propose a pathogenic model in which the alarmin cytokine, interleukin (IL)-33, is a key player in driving all stages of COVID-19 disease (ie, asymptomatic, mild–moderate, severe–critical, and chronic–fibrotic). In susceptible individuals, IL-33 release by damaged lower respiratory cells might induce dysregulated GATA-binding factor 3-expressing regulatory T cells, thereby breaking immune tolerance and eliciting severe acute respiratory syndrome coronavirus 2-induced autoinflammatory lung disease. Such disease might be initially sustained by IL-33-differentiated type-2 innate lymphoid cells and locally expanded γδ T cells. In severe COVID-19 cases, the IL-33–ST2 axis might act to expand the number of pathogenic granulocyte–macrophage colony-stimulating factor-expressing T cells, dampen antiviral interferon responses, elicit hyperinflammation, and favour thromboses. In patients who survive severe COVID-19, IL-33 might drive pulmonary fibrosis by inducing myofibroblasts and epithelial–mesenchymal transition. We discuss the therapeutic implications of these hypothetical pathways, including use of therapies that target IL-33 (eg, anti-ST2), T helper 17-like γδ T cells, immune cell homing, and cytokine balance.

CircRNAs in Lung-intestinal Axis Cancer.

The "exterior-interior relationship between the lung and the large intestine" is a basic theory in Traditional Chinese Medicine (TCM), which has been confirmed by mounting evidence, and the lung-intestinal axis can be seen as an extension of this theory. Circular RNAs (circRNAs) are a kind of conserved and structurally stable noncoding RNAs, which have been found to be differentially expressed and associated with the development of cancer in malignant tumors. Many studies have found that circRNAs play an important role in lung and intestinal cancers. This review focuses on circRNAs and reveals that there are common circRNAs that are both highly or poorly expressed in lung-intestinal axis cancers and most of them regulate the proliferation, migration, and invasion of cancer cells by sponging miRNAs. These results not only provide new evidence and research ideas for the "exterior-interior relationship between the lung and the large intestine", but also suggest that circRNAs can be new potential therapeutic targets for the future drug research of lung-intestinal axis diseases.

Blockade of SARS-CoV-2 infection by recombinant soluble ACE2

Viruses use specific host-cell plasma membrane molecules as receptors to enter the cell. SARS-CoV-2, the coronavirus responsible for the current COVID-19 pandemic, is believed to bind mainly or exclusively to angiotensin-converting enzyme 2 (ACE2), a cell-surface protein otherwise known for its enzymatic, carboxypeptidase-type activity and its physiological role in the renin-angiotensin system.1,2 ACE2 activity per se does not seem to be involved in infectivity, but its role in lung, heart, and kidney function has putative consequences for disease severity.

The Critical appraisal of pipasa in chronic obstructive pulmonary disease

The Srotas are well defined concept explained by Acharya Sushruta and Charak; Udakvaha Srotas is one of them. Its root source (Moolsthan) is Talu &amp; Kloma. The root source Talu of Udakvaha Srotas is well known and understood as palate everywhere but still there is ambiguity about Kloma. The thirst (Pipasa) is prime symptom of interruption in Udakvaha Srotas similarly thirst is also found in chronic obstructive pulmonary disease (COPD) cases, therefore it would be possible to study the role of lungs in maintenance of water in the body. So, this was primary effort to study the structure Kloma in the body with the help of observational study i.e. by observing Pipasa in cases of COPD considering the lung as a controversial structure Kloma. Secondary objectives of the study were literature search about Kloma, study of Viddha Lakshana and correlation of Kloma with present well-known structure. So to explain the anatomical area of Kloma and specify Kloma with body organ was the prime plan to start this review.

The Role of Lung and Gut Microbiota in The Combat Against COVID-19

İlk defa 2019 Aralık ayında Çin’in Wuhan şehrinde görülen ve kısa sürede bir salgına neden olan COVID-19 11 Mart 2020'de Dünya Sağlık Örgütü (WHO) tarafından küresel salgın olarak ilan edilmiştir. Hastalık özellikle bağışıklık sistemi problemleri başta olmak üzere diyabet, kalp hastalıkları gibi diğer kronik hastalıkları olan kişilerde ciddi bir klinik seyir göstermektedir. Virüslere karşı savunmada immün sistemin fonksiyonları ve modülasyonu son derece önemlidir. Birçok araştırmanın sonuçlarına göre, doğal immün sistemi güçlendirmenin yollarından biri de bağırsak mikrobiyotasını dengelemektir. Son zamanlarda yapılan çalışmalar akciğer mikrobiyotası ile bağırsak mikrobiyotasının ilişkili olduğunu ve mikrobiyota dengesinin viral solunum yolu hastalıklarının önlenmesi ve savunmasında önemli olabileceğini göstermektedir. COVID-19’a karşı etkin bir tedavi ve aşı geliştirmek için tüm Dünya’da bilim adamları yoğun olarak çalışmaktadır, ancak henüz kesin tedavisi ya da aşısı bulunamamıştır. Covid-19 hastalığı sürecinde fonksiyonel tıp bakış açısıyla fizyopatolojik mekanizmalara yönelik geliştirilecek yeni profilaktik yaklaşımlar ve tedavi protokollerine ihtiyaç vardır. Bağırsak ve akciğer mikrobiyotaların düzenlenmesinin immün sistemi güçlendirerek korunmada önemli olabileceği, yanı sıra tedavi protokollerinde bir tedavi hedefi olarak yer alabileceğini ileri sürülmektedir. COVID-19 salgını, sağlıklı yaşam, sağlığın korunması, güçlendirme ve bağışıklık sistemi modülasyonu gibi profilaktik yaklaşımların önemini bir kez daha göstermiştir. Mikrobiyota kaynaklarının nasıl elde edilip kullanılacağı, mikrobiyota düzenleyici-destekleyici ürünlerin uygulamasının standardizasyonu ve beslenmenin düzenlenmesinin tedavideki rolü gibi pek çok konuda ileri araştırmalara ihtiyaç vardır.

Lung Disease Diagnostic Model Through IgG Sensitization to Microbial Extracellular Vesicles.

PurposeRecently, there has been a rise in the interest to understand the composition of indoor dust due to its association with lung diseases such as asthma, chronic obstructive pulmonary disease (COPD) and lung cancer. Furthermore, it has been found that bacterial extracellular vesicles (EVs) within indoor dust particles can induce pulmonary inflammation, suggesting that these might play a role in lung disease.MethodsWe performed microbiome analysis of indoor dust EVs isolated from mattresses in apartments and hospitals. We developed diagnostic models based on the bacterial EVs antibodies detected in serum samples via enzyme-linked immunosorbent assay (ELISA) in this analysis.ResultsProteobacteria was the most abundant bacterial EV taxa observed at the phylum level while Pseudomonas, Enterobacteriaceae (f) and Acinetobacter were the most prominent organisms at the genus level, followed by Staphylococcus. Based on the microbiome analysis, serum anti-bacterial EV immunoglobulin G (IgG), IgG1 and IgG4 were analyzed using ELISA with EV antibodies that targeted Staphylococcus aureus, Acinetobacter baumannii, Enterobacter cloacae and Pseudomonas aeruginosa. The levels of anti-bacterial EV antibodies were found to be significantly higher in patients with asthma, COPD and lung cancer compared to the healthy control group. We then developed a diagnostic model through logistic regression of antibodies that showed significant differences between groups with smoking history as a covariate. Four different variable selection methods were compared to construct an optimal diagnostic model with area under the curves ranging from 0.72 to 0.81.ConclusionsThe results of this study suggest that ELISA-based analysis of anti-bacterial EV antibodies titers can be used as a diagnostic tool for lung disease. The present findings provide insights into the pathogenesis of lung disease as well as a foundation for developing a novel diagnostic methodology that synergizes microbial EV metagenomics and immune assays.

Guanine Content of MicroRNAs is Associated with their Tumor- Suppressive and Oncogenic Roles in Lung and Breast Cancers.

microRNAs (miRNAs, miRs) are small noncoding RNAs that negatively regulate gene expression at the post-transcriptional level and fine-tune gene functions. Global repression of miRNAs expression in different types of human tumors, after exposure to cigarette smoke, or to the hormone estrogen, have been shown to be associated with guanine (G) enrichment in the terminal Loops (TLs) of their precursors. We integrated the G content of miRNA mature forms and precursor miRNA TLs with their described function in the literature, using the PubMed database. Gene Ontology term analysis was used to describe the pathways in which the G-enriched miRNA targets are involved. Herein, we show an association between the relative G enrichment of precursor miRNAs' TLs and their tendency to act as tumor suppressor miRs in human lung and breast cancers. Another association was observed between the high G content of the miRNAs 5-mature forms and their tendency to act as oncomiRs. The results support previous findings showing that the G sequence content is an important feature determining miRNA expression and function, and opens the way for future cancer investigations in this direction.

Identification of nicotinic acetylcholine receptor subunits in different lung cancer cell lines and the inhibitory effect of alpha-conotoxin TxID on lung cancer cell growth

Lung cancer is an aggressive tumor with high incidence and mortality rate. There was growing evidence supporting that nicotinic acetylcholine receptors (nAChRs) play vital role inlung cancer development. In this study, the expression of α3, α4, α5, α6, α7, α9, α10, β2, β3, β4 nAChR subunits on protein and mRNA level were studied in A549, NCI–H1299, NCI–H1688, DMS114 and normal human embryonic lung fibroblast (HEL) cell lines by real-time quantitative PCR (qPCR) and Western blot assay respectively. The results indicated that most of these nAChR subunits were expressed in these five cell lines. Compared with normal cells, the expression of α3 and β4 nAChR subunits were upregulated in A549 and NCI–H1299. Thus, we treated A549 and NCI–H1299 with an antagonist α-conotoxin TxID which potently and selectively blocks α3β4 nAChRs. TxID treatment could inhibit A549 and NCI–H1299 cell growth and enhance the inhibitory effect of adriamycin when treated simultaneously. To sum up, our study identified the expression of nAChR subunits in different lung cells and the anti-tumor effect of α-conotoxin TxID, which may provide novel strategies for lung cancer therapy.

Analysis of Ultrastructural Properties Reveals SP-D Protective Roles in Lung and Pancreatic Injury of Severe Acute Pancreatitis in Mouse Model

Analysis of Ultrastructural Properties Reveals SP-D Protective Roles in Lung and Pancreatic Injury of Severe Acute Pancreatitis in Mouse Model

The role of lung ultrasound in diagnosis of critical lung illness in newborn infants

The chest x-rays and CT scanning are the first choice among the common diagnosing tools in lung diseases of newborn infants, but the chest x-rays to diagnose critical illness lack accuracy and it may cause ionizing radiation.Lung ultrasound shows high sensitivity and specificity in the diagnosing of neonatal respiratory distress syndrome, transient tachypnea of newborn and pneumothorax.Lung ultrasound has been proved to be more favorable in neonatal critical illness.Basic signs of lung ultrasound include A-line, lung sliding, seashore sign, B-line, lung rockets, et al. Key words: Lung ultrasound; Newborn; Critical illness

Downregulation of Alloimmunity in Lung Allograft by Eosinophils is Orchestrated by PD-L1 Dependent Contact with CD8+ T Cells

Purpose Eosinophils play a surprising role in lung allograft-specific tolerance induction dependent on the blockade of the CD40 and CD28 stimulatory pathways (CSB). The mechanisms used by eosinophils to downregulate the alloimmune response remains elusive. Methods To study the mechanism of eosinophil-dependent immune responses fully MHC-mismatched Balb/c (H2Kd) lungs were engrafted to C57BL/6J (H2Kb) recipients without immunosuppression. For some experiments eosinophils were ablated through the administration of diphtheria toxin (DT) to C57BL/6 mice expressing DTR on an eosinophil-peroxidase specific promoter (iPHIL mice). To model alloreactivity in vitro, mixed leukocyte cultures, comprising Th1-polarized (E1) eosinophils as modulators of T cells from C57BL/6J mice stimulated by either allogeneic dendritic cells or anti-CD3/CD28 agonistic antibodies. Results Lung graft-resident eosinophils demonstrated a Th1 polarized phenotype (or E1 polarization) in the presence or absence of CSB. In the absence of CSB eosinophils express higher levels of MHC-1 and PD-L1. Ablation of eosinophils in non-immunosuppressed graft recipients enhances T cell activation with higher ISHLT rejection grade (p Conclusion We demonstrate that even without immunosuppression, eosinophils contribute to the downregulation of alloimmunity. Eosinophils upregulate PD-L1 and use this mechanism to mediate contact-dependent downregulation of T cell activation. We also show that mobilization of eosinophils into the lung allograft through intra-tracheal instillation of eotaxins and IL-5 can be utilized to downregulate the alloimmune response and sets the stage for unique and previously unexplored strategies for tolerance induction.

Transthoracic lung and pleura ultrasonography as a diagnostic tool of pulmonary edema in dogs and cats

Despite the consensus on the role of lung and pleura ultrasound in human medicine, veteri- nary medicine questions credibility of the pulmonary evaluation in ultrasound examination, based on the analysis of artifacts in animals with clinical signs of respiratory failure and possibility of pulmonary edema diagnosis with recognition of the degree of its severity. The study was conduct- ed on 47 animals (29 dogs and 18 cats) of different breeds, age and sex. In all of animals prior to the transthoracic lung and pleura ultrasound examination (TLPUS), all animals were subjected to a clinical examination and hematological blood test as well as chest radiography examination in three projections. Ultrasound imaging of the chest in each animal was performed at designated four defined segments. TLPUS in dogs and cats based on an analysis of artifacts allows recogni- tion of pulmonary edema, to the degree comparable to chest X-ray examination. The number of depicted B-lines artifacts is proportional to the degree of pulmonary edema. These results allow to reduce the number of radiographs and allow the shortening of the diagnostic process for pa- tients in life-threatening condition.

Investigating the antibacterial effect of Sca1+ lung mesenchymal stem cells on multidrug resistant bacterial species

Abstract Rationale Although bone marrow-derived mesenchymal stem cells have been extensively studied in host protection against bacterial pneumonia, the role of lung stem/mesenchymal stem cells in pneumonia caused by the multidrug-resistant bacteria remains elusive. Methods We have compared the extracellular (using 10 MOI) and intracellular (using 1 MOI) killing effects of stem cell antigen 1+ lung mesenchymal stem cells (Sca1+ LMSC), bone marrow-derived neutrophils (BMDN), and bone marrow-derived macrophages (BMDM) by infecting them with Gram positive methicillin-resistant Staphylococcus aureus (MRSA) and Gram negative carbapenem-resistant Klebsiella pneumoniae (CRKP) at different time points. We evaluated the extracellular and intracellular killing at each time point by plating them on Tryptic soy agar and MacConkey agar plates, respectively. We also have examined expression of inflammasomes or inflammasome-associated proteins in MRSA (20 MOI for 6 h) infected LMSC using Western blotting. Results Sca1+ LMSC is potent in killing (extracellular) both MRSA and CRKP at 3 h post-infection. However, BMDN did not show significant extracellular killing on MRSA and CRKP at all time points examined. Interestingly, Sca1+ LMSC showed a remarkably increased intracellular killing of MRSA than BMDM. Western blotting revealed the increased level of inflammasome and inflammasome-associated proteins (NLRP3, NLRP6 and ASC) in MRSA infected LMSC. Conclusions These findings have solidified the potential of LMSC-based therapies for pneumonia caused by MRSA and CRKP. However, in vivo (animal) studies are required to determine the effectiveness of LMSC in the clearance of these bacteria and modulation of innate immune responses in the host.

GLI2 promoter hypermethylation in saliva of children with a respiratory allergy

BackgroundThe prevalence of respiratory allergy in children is increasing. Epigenetic DNA methylation changes are plausible underlying molecular mechanisms.ResultsSaliva samples collected in substudies of two longitudinal birth cohorts in Belgium (FLEHS1 & FLEHS2) were used to discover and confirm DNA methylation signatures that can differentiate individuals with respiratory allergy from healthy subjects. Genome-wide analysis with Illumina Methylation 450K BeadChips revealed 23 differentially methylated gene regions (DMRs) in saliva from 11y old allergic children (N=26) vs. controls (N=20) in FLEHS1. A subset of 7 DMRs was selected for confirmation by iPLEX MassArray analysis. First, iPLEX analysis was performed in the same 46 FLEHS1 samples for analytical confirmation of the findings obtained during the discovery phase. iPLEX results correlated significantly with the 450K array data (P <0.0001) and confirmed 4 out of the 7 DMRs. Aiming for additional biological confirmation, the 7 DMRs were analyzed using iPLEX in a substudy of an independent birth cohort (FLEHS2; N=19 cases vs. 20 controls, aged 5 years). One DMR in the GLI2 promoter region showed a consistent statistically significant hypermethylation in individuals with respiratory allergy across the two birth cohorts and technologies. In addition to its involvement in TGF-β signaling and T-helper differentiation, GLI2 has a regulating role in lung development.ConclusionGLI2 is considered an interesting candidate DNA methylation marker for respiratory allergy.

Mechanosensing Piezo channels in tissue homeostasis including their role in lungs

Piezo channels are deemed to constitute one of the most important family of mechanosensing ion channels since their discovery in 2010. With recent advances in identifying their topological structure and the discovery of the agonist Yoda1 as well as the specific inhibitor GsMTx4, it is now possible to study the mechanisms by which Piezo channels are involved in physiological and pathophysiological processes. During embryonic cardiovascular development, Piezo1 senses shear stress and promotes vasculature growth. In adult mice, Piezo1 mediates the release of nitric oxide and ATP from endothelial cells to regulate blood pressure. Piezo channels also play a crucial role in cell differentiation and tissue homeostasis by exquisite mechanical force sensing.Piezo channels are also abundantly expressed in lung tissues. As the lung is exposed to complex pulmonary hemodynamics and respiratory mechanics, cells in the lung, such as microvascular endothelial cells, bear mechanical forces from blood flow shear, pulsatile strain, static pressure, and cyclic stretch due to respiratory movement. These mechanical stimuli are involved in a serial of physiological function and pathophysiological processes of the lung, many of which Piezo channels may be the key player. Mutation of genes encoding Piezo channels are also associated with hereditary human diseases, thus highlighting the critical role of Piezo channels in both tissue homeostasis and disease.