1. Academic Validation
  2. Protein nanoparticle-induced osmotic pressure gradients modify pulmonary edema through hyperpermeability in acute respiratory distress syndrome

Protein nanoparticle-induced osmotic pressure gradients modify pulmonary edema through hyperpermeability in acute respiratory distress syndrome

  • J Nanobiotechnology. 2022 Jul 6;20(1):314. doi: 10.1186/s12951-022-01519-1.
ZhiZhi Qian  # 1 2 QianYi Wang  # 1 2 ZhaoShun Qiu 1 2 DanYang Li 1 2 ChenCheng Zhang 1 2 XiYu Xiong 1 2 ZiHui Zheng 1 2 QinLi Ruan 1 2 YiChen Guo 3 Jun Guo 4 5
Affiliations

Affiliations

  • 1 School of Medicine & Holistic Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing, 210023, Jiangsu, People's Republic of China.
  • 2 Key Laboratory of Drug Target and Drug for Degenerative Disease, Nanjing University of Chinese Medicine, Nanjing, 210023, Jiangsu, People's Republic of China.
  • 3 Biomedical Engineering, University of Alabama at Birmingham School of Medicine, Birmingham, AL, USA. [email protected].
  • 4 School of Medicine & Holistic Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing, 210023, Jiangsu, People's Republic of China. [email protected].
  • 5 Key Laboratory of Drug Target and Drug for Degenerative Disease, Nanjing University of Chinese Medicine, Nanjing, 210023, Jiangsu, People's Republic of China. [email protected].
  • # Contributed equally.
Abstract

Acute respiratory distress syndrome (ARDS), caused by noncardiogenic pulmonary edema (PE), contributes significantly to Coronavirus 2019 (COVID-19)-associated morbidity and mortality. We explored the effect of transmembrane osmotic pressure (OP) gradients in PE using a fluorescence resonance energy transfer-based Intermediate filament (IF) tension optical probe. Angiotensin-II- and bradykinin-induced increases in intracellular protein nanoparticle (PN)-OP were associated with inflammasome production and cytoskeletal depolymerization. Intracellular protein nanoparticle production also resulted in cytomembrane hyperpolarization and L-VGCC-induced calcium signals, which differed from diacylglycerol-induced calcium increment via TRPC6 activation. Both pathways involve voltage-dependent cation influx and OP upregulation via SUR1-TRPM4 channels. Meanwhile, intra/extracellular PN-induced OP gradients across membranes upregulated pulmonary endothelial and alveolar barrier permeability. Attenuation of intracellular PN, calcium signals, and cation influx by drug combinations effectively relieved intracellular OP and pulmonary endothelial nonselective permeability, and improved epithelial fluid absorption and PE. Thus, PN-OP is pivotal in pulmonary edema in ARDS and COVID-19, and transmembrane OP recovery could be used to treat pulmonary edema and develop new drug targets in pulmonary injury.

Keywords

ARDS; Multi-targeted blockade; Protein nanoparticle-induced osmotic pressure; Pulmonary edema; Voltage-dependent ion channels.

Figures
Products
Inhibitors & Agonists
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-100720
    99.74%, TRPV4 Antagonist
Other Products