DRD1 downregulation contributes to mechanical stretch-induced lung endothelial barrier dysfunction

Wang, Yan; Liu, Yujian; Xu, Dun‐Feng; Zhang, Hui; Xu, Chang; Mao, Yanfei; Zhou, Lv; Zhu, Xiaoyan; Jiang, Lai

doi:10.7150/thno.46192

Cited by 13 publications

(8 citation statements)

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“…Dopamine D1 receptor (DRD1) is downregulated in both surgical patients and mice exposed to mechanical ventilation. The administration of DRD1 agonist attenuates the mechanical stretch-induced lung endothelial barrier dysfunction by inhibiting deacetylation of α-Tubulin via cAMP/EPAC/HDAC6 signaling pathway (Wang Y. et al, 2021). Vascular homeostasis is regulated by normal shear stress sensing and barrier function, which are controlled by the adherens junctions (Stanicek et al, 2020).…”

Section: Endothelial Permeability Impairment Causes Fluid Leakingmentioning

confidence: 99%

Mechanotransduction Regulates the Interplays Between Alveolar Epithelial and Vascular Endothelial Cells in Lung

et al. 2022

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Mechanical stress plays a critical role among development, functional maturation, and pathogenesis of pulmonary tissues, especially for the alveolar epithelial cells and vascular endothelial cells located in the microenvironment established with vascular network and bronchial-alveolar network. Alveolar epithelial cells are mainly loaded by cyclic strain and air pressure tension. While vascular endothelial cells are exposed to shear stress and cyclic strain. Currently, the emerging evidences demonstrated that non-physiological mechanical forces would lead to several pulmonary diseases, including pulmonary hypertension, fibrosis, and ventilation induced lung injury. Furthermore, a series of intracellular signaling had been identified to be involved in mechanotransduction and participated in regulating the physiological homeostasis and pathophysiological process. Besides, the communications between alveolar epithelium and vascular endothelium under non-physiological stress contribute to the remodeling of the pulmonary micro-environment in collaboration, including hypoxia induced injuries, endothelial permeability impairment, extracellular matrix stiffness elevation, metabolic alternation, and inflammation activation. In this review, we aim to summarize the current understandings of mechanotransduction on the relation between mechanical forces acting on the lung and biological response in mechanical overloading related diseases. We also would like to emphasize the interplays between alveolar epithelium and vascular endothelium, providing new insights into pulmonary diseases pathogenesis, and potential targets for therapy.

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Section: Endothelial Permeability Impairment Causes Fluid Leakingmentioning

confidence: 99%

Mechanotransduction Regulates the Interplays Between Alveolar Epithelial and Vascular Endothelial Cells in Lung

et al. 2022

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“…The lung injury score was assessed by two pathologists with expertise in lung pathology. The criteria for scoring lung injury were set up as previously described (24,25): 0 = normal tissue; 1 = tiny inflammatory change; 2 = mild to moderate inflammatory changes without marked damage in the lung architecture; 3 = moderate inflammatory injury with thickening of the alveolar septa; 4 = moderate to severe inflammatory injury with the formation of nodules or areas of pneumonitis; and 5 = severe inflammatory injury with total obliteration of the field. The mean score was reported per section.…”

Section: Histopathological Evaluation Of the Lung Tissuementioning

confidence: 99%

Upregulation of FOXO1 contributes to lipopolysaccharide-induced pulmonary endothelial injury by induction of autophagy

Zhao¹,

Zhang²,

Zhang³

et al. 2022

Ann Transl Med

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Background: Autophagy is activated during the pathogenesis of endothelial dysfunction and sepsisassociated acute lung injury (ALI). This study aimed to investigate whether autophagy affected endothelial barrier dysfunction and lung injury in a murine model of lipopolysaccharide (LPS)-induced ALI, and then further clarify whether forkhead box O1 (FOXO1), an autophagy-related transcriptional factor, contributed to autophagy activation and ALI induced by LPS.Methods: Male C57BL/6 mice were treated with LPS (30 mg/kg), and then were allocated to a control group and an LPS group with or without FOXO1 inhibitor (AS1842856) treatment, respectively. Primary cultured mouse lung vascular endothelial cells (MLVECs) were treated with LPS, autophagy inhibitor 3-methyladenine (3-MA), AS1842856, and small interfering RNA (siRNA) targeting autophagy-related gene 5 (ATG5) or FOXO1. Endothelial autophagic flux was assessed by transfection of MLVECs with red fluorescent protein (RFP)-green fluorescent protein (GFP) tandem fluorescent-tagged LC3 (RFP-GFP-LC3) adenovirus. Endothelial permeability was analyzed by the diffusion of fluorescein isothiocyanatecarboxymethyl (FITC)-dextran through the endothelial monolayer. Evans blue albumin tracer was used to measure the pulmonary transvascular permeability, and hematoxylin and eosin (H&E) staining was used to observe pathological changes in the lung tissues. Immunofluorescence staining was also used to detect the expression of zonula occludens-1 (ZO-1) and FOXO1. Results: This study found autophagy induction in lung tissues of endotoxemic mice and LPS-treated MLVECs, as evidenced by elevated expression of light chain 3 II (LC3-II) and Unc-51-like kinase (ULK1) and autophagic flux. LPS treatment decreased vascular endothelial (VE)-cadherin and ZO-1 expression and increased endothelial permeability in MLVECs, which were significantly alleviated by autophagy inhibitor 3-MA and ATG5 siRNA. It was found that both phosphorylated FOXO1 and FOXO1 were upregulated in the lung tissues of endotoxemic mice and LPS-treated MLVECs. Both FOXO1 inhibitor AS1842856 and FOXO1 siRNA suppressed LPS-induced autophagy and endothelial cell injury in MLVECs. Moreover, FOXO1 inhibition profoundly alleviated autophagy, lung endothelial hyperpermeability, and ALI in endotoxemic mice.Conclusions: This work demonstrated that FOXO1 upregulation is an important contributor to LPS-

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“…Under high blood pressure, cyclic strain on vascular cell increases vascular wall thickness and facilitates reactive oxygen species (ROS) generation [ 25 ]. Similar to the vessel, cyclic stretch in the lung stimulates local fibroblast and macrophage change biochemical microenvironment [ 26 ]. In addition to the influence on cell physiological status, mechanical strain is also involved in the tissue regeneration process.…”

Section: Mechanical Strainmentioning

confidence: 99%

Mechanical Cues Regulate Histone Modifications and Cell Behavior

Zhou

Wang

et al. 2022

Stem Cells International

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Change of biophysical factors in tissue microenvironment is an important step in a chronic disease development process. A mechanical and biochemical factor from cell living microniche can regulate cell epigenetic decoration and, therefore, further induce change of gene expression. In this review, we will emphasize the mechanism that biophysical microenvironment manipulates cell behavior including gene expression and protein decoration, through modifying histone amino acid residue modification. The influence given by different mechanical forces, including mechanical stretch, substrate surface stiffness, and shear stress, on cell fate and behavior during chronic disease development including tumorigenesis will also be teased out. Overall, the recent work summarized in this review culminates on the hypothesis that a mechanical factor stimulates the modification on histone which could facilitate disease detection and potential therapeutic target.

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DRD1 downregulation contributes to mechanical stretch-induced lung endothelial barrier dysfunction

Cited by 13 publications

References 0 publications

Mechanotransduction Regulates the Interplays Between Alveolar Epithelial and Vascular Endothelial Cells in Lung

Mechanotransduction Regulates the Interplays Between Alveolar Epithelial and Vascular Endothelial Cells in Lung

Upregulation of FOXO1 contributes to lipopolysaccharide-induced pulmonary endothelial injury by induction of autophagy

Mechanical Cues Regulate Histone Modifications and Cell Behavior

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