ArticleAmerican journal of physiology. Lung cellular and molecular physiology2011
Activation of hypoxia-inducible factor-1 protects airway epithelium against oxidant-induced barrier dysfunction.
Article in American journal of physiology. Lung cellular and molecular physiology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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Who cites it
44 citing papers in PubMed, 82 citations in OpenAlex.
- Hypoxia: a critical pathophysiological driver in respiratory inflammatory diseases.Military Medical Research · 2026Review
- A Novel Therapeutic Target for Pediatric Pneumonia: Sestrin2.Medicina (Kaunas, Lithuania) · 2025Article
- Review
- Influence of Hypoxia on the Airway Epithelium.Physiological research · 2024Review
- Sestrin2 serves as a scaffold protein to maintain cardiac energy and metabolic homeostasis during pathological stress.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2024Review
- Role of sestrins in metabolic and aging-related diseases.Biogerontology · 2024Review
- Sestrin2 as a Protective Shield against Cardiovascular Disease.International journal of molecular sciences · 2023Review
- Sestrin2: multifaceted functions, molecular basis, and its implications in liver diseases.Cell death & disease · 2023Review
- Peroxiredoxins and Hypoxia-Inducible Factor-1α in Duodenal Tissue: Emerging Factors in the Pathophysiology of Pediatric Celiac Disease Patients.Current issues in molecular biology · 2023Article
- Liquid application dosing alters the physiology of air-liquid interface (ALI) primary human bronchial epithelial cell/lung fibroblast co-cultures andFrontiers in toxicology · 2023Article
- Inhibition of hypoxia-inducible factor-prolyl hydroxylation protects from cyclophosphamide-induced bladder injury and urinary dysfunction.American journal of physiology. Renal physiology · 2022Article
- HIF-1α Stabilization in Flagellin-Stimulated Human Bronchial Cells Impairs Barrier Function.Cells · 2022Article
- The functions and roles of sestrins in regulating human diseases.Cellular & molecular biology letters · 2022Review
- Perioperative Pulmonary Atelectasis: Part I. Biology and Mechanisms.Anesthesiology · 2022Review
- Sestrin2 in hypoxia and hypoxia-related diseases.Redox report : communications in free radical research · 2021Review
- Potential Roles of Sestrin2 in Alzheimer's Disease: Antioxidation, Autophagy Promotion, and Beyond.Biomedicines · 2021Review
- Review
- Elevating sestrin2 attenuates endoplasmic reticulum stress and improves functional recovery through autophagy activation after spinal cord injury.Cell biology and toxicology · 2021Article
- Sestrin2 as a gatekeeper of cellular homeostasis: Physiological effects for the regulation of hypoxia-related diseases.Journal of cellular and molecular medicine · 2021Review
- Can efficient stimulation of myogenic microcirculatory oscillations by transient ischemia predict low incidence of COVID-19 infection?Respiratory physiology & neurobiology · 2021Article
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
The respiratory epithelium forms an important barrier against inhaled pollutants and microorganisms, and its barrier function is often compromised during inflammatory airway diseases. Epithelial activation of hypoxia-inducible factor-1 (HIF-1) represents one feature of airway inflammation, but the functional importance of HIF-1 within the respiratory epithelium is largely unknown. Using primary mouse tracheal epithelial (MTE) cells or immortalized human bronchial epithelial cells (16HBE14o-), we evaluated the impact of HIF-1 activation on loss of epithelial barrier function during oxidative stress. Exposure of either 16HBE14o- or MTE cells to H(2)O(2) resulted in significant loss of transepithelial electrical resistance and increased permeability to fluorescein isothiocyanate-dextran (4 kDa), and this was attenuated significantly after prior activation of HIF-1 by preexposure to hypoxia (2% O(2); 6 h) or the hypoxia mimics CoCl(2) or dimethyloxalylglycine (DMOG). Oxidative barrier loss was associated with reduced levels of the tight junction protein occludin and with hyperoxidation of the antioxidant enzyme peroxiredoxin (Prx-SO(2)H), events that were also attenuated by prior activation of HIF-1. Involvement of HIF-1 in these protective effects was confirmed using the pharmacological inhibitor YC-1 and by short-hairpin RNA knockdown of HIF-1α. The protective effects of HIF-1 were associated with induction of sestrin-2, a hypoxia-inducible enzyme known to reduce oxidative stress and minimize Prx hyperoxidation. Together, our results suggest that loss of epithelial barrier integrity by oxidative stress is minimized by activation of HIF-1, in part by induction of sestrin-2.
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