Abstract
Background
Ischemia-reperfusion injury (IRI), which involves severe inflammation and edema, is
an inevitable feature of the lung transplantation process and leads to primary graft
dysfunction (PGD). The activation of aquaporin 1 (AQP1) modulates fluid transport
in the alveolar space. The current study investigated the role of AQP1 in ischemia-reperfusion
(IR)-induced lung injury.
Methods
A mouse model of lung IR was established by clamping the left lung hilar for 1 h and
released for reperfusion for 24 h. The AQP1 inhibitor acetazolamide (AZA) was administered
3 days before lung ischemia with a dose of 100 mg/kg per day via gavage. Lung injury
was evaluated using the ratio of wet-to-dry weight, peripheral bronchial epithelial
thickness, degree of angioedema, acute lung injury score, neutrophil infiltration,
and cytokine concentrations in bronchoalveolar lavage fluid.
Results
Compared with sham treatment, ischemia with no reperfusion (IR 0h) and ischemia with
reperfusion for 24 h (IR 24 h) significantly upregulated AQP1 expression, increased
the wet/dry weight ratio, angioedema, neutrophil infiltration and cytokine production
(interleukin -6 and tumor necrosis factor -α) and thickened the peripheral bronchial
epithelium. AZA exacerbated inflammation and pulmonary edema.
Conclusion
AQP1 may exert a protective effect against IR-induced lung injury, which could be
attributed to alleviating pulmonary edema and inflammation. AQP1 upregulation might
be a potential application to alleviate lung IRI and decrease the incidence of PGD.
Keywords
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References
- Current trends in thoracic surgery.Nagoya J Med Sci. 2020; 82: 161-174
- Primary graft dysfunction.Semin Respir Crit Care Med. 2021; 42: 368-379
- Liberalization of donor criteria may expand the donor pool without adverse consequence in lung transplantation.J Heart Lung Transplant. 2000; 19: 1199-1204
- Primary graft dysfunction.Curr Opin Organ Transplant. 2021; 26: 321-327
- Longitudinal quantification of radical bursts during pulmonary ischaemia and reperfusion conference discussion.Eur J Cardio-Thorac. 2015; 48: 628-629
- Ischemia-reperfusion injury in the transplanted lung: a literature review.Transplant Direct. 2021; 7: e652
- The aquaporin water channels.Proc Am Thorac Soc. 2006; 3: 5-13
- Agmatine attenuates brain edema through reducing the expression of aquaporin-1 after cerebral ischemia.J Cerebr Blood F Met. 2010; 30: 943-949
- Ischemia-reperfusion alters the immunolocalization of glial aquaporins in rat retina.Neurosci Lett. 2006; 408: 108-112
- Testicular AQP1 expression in a rat model of testicular ischemiae-reperfusion injury.J Pediatr Urol. 2021; 17
- Aquaporin-4 expression in post-traumatic syringomyelia.J Neurotrauma. 2013; 30: 1457-1467
- Activation of TGR5 restores AQP2 expression via the HIF pathway in renal ischemia-reperfusion injury.Am J Physiol Renal Physiol. 2021; 320: F308-FF21
- Aquaporin 1 alleviates acute kidney injury via PI3K-mediated macrophage M2 polarization.Inflamm Res. 2020; 69: 509-521
- Aquaporins in the lung.Pflugers Arch. 2019; 471: 519-532
- Higher expression levels of aquaporin (AQP)1 and AQP5 in the lungs of arid-desert living Lepus yarkandensis.J Anim Physiol Anim Nutr (Berl). 2020; 104: 1186-1195
- Polarized distribution of key membrane transport proteins in the rat submandibular gland.Pflugers Arch. 1997; 433: 260-268
- Role of aquaporin-4 in airspace-to-capillary water permeability in intact mouse lung measured by a novel gravimetric method.J Gen Physiol. 2000; 115: 17-27
- Transcellular water transport in lung alveolar epithelium through mercury-sensitive water channels.Proc Natl Acad Sci USA. 1994; 91: 4970-4974
- Ischemic postconditioning alleviates lung injury and maintains a better expression of aquaporin-1 during cardiopulmonary bypass.Chin Med J (Engl). 2014; 127: 4012-4018
- Expression of aquaporin-1 and aquaporin-3 in lung tissue of rat model with ischemia-reperfusion injury.Chin Med J (Engl). 2010; 123: 3711-3713
- COX-2 inhibition attenuates lung injury induced by skeletal muscle ischemia reperfusion in rats.Int Immunopharmacol. 2016; 31: 116-122
- Influence of extract of Ginkgo biloba leaves tablets on the aquaporin-1 expression in isolated lung ischemia reperfusion.Chin Med J (Engl). 2013; 126: 4720-4723
- Expression of aquaporin-1 and aquaporin-3 in lung tissue of rat model with ischemia-reperfusion injury.Chin Med J-Peking. 2010; 123: 3711-3713
- Models of lung transplant research: a consensus statement from the national heart, lung, and blood institute workshop.JCI Insight. 2017; 2
- Acetazolamide inhibits osmotic water permeability by interaction with aquaporin-1.Anal Biochem. 2006; 350: 165-170
- Comparative efficacy of HgCl2 with candidate aquaporin-1 inhibitors DMSO, gold, TEA+ and acetazolamide.FEBS Lett. 2006; 580: 6679-6684
- Pirfenidone alleviates lung ischemia-reperfusion injury in a rat model.J Thorac Cardiovasc Surg. 2019; 158: 289-296
- An official American thoracic society workshop report: features and measurements of experimental acute lung injury in animals.Am J Respir Cell Mol Biol. 2011; 44: 725-738
- Increased lung ischemia-reperfusion injury in aquaporin 1-null mice is mediated via decreased hypoxia-inducible factor 2alpha stability.Am J Respir Cell Mol Biol. 2016; 54: 882-891
- Aquaporin water channels and lung physiology.Am J Physiol Lung Cell Mol Physiol. 2000; 278: L867-L879
- Reduced lung water transport rate associated with downregulation of aquaporin-1 and aquaporin-5 in aged mice.Clin Exp Pharmacol Physiol. 2009; 36: 734-738
- Effects of different resuscitation fluids on pulmonary expression of aquaporin1 and aquaporin5 in a rat model of uncontrolled hemorrhagic shock and infection.PLoS One. 2013; 8: e64390
- Expression of aquaporin-1 and aquaporin-5 in a rat model of high-altitude pulmonary edema and the effect of hyperbaric oxygen exposure.Dose Resp. 2020; 181559325820970821
- Acute respiratory distress syndrome.N Engl J Med. 2017; 377: 562-572
- Ischemia-reperfusion injury in lung transplantation.Cells. 2021; 10: 1333
- Induced expression and functional effects of aquaporin-1 in human leukocytes in sepsis.Crit Care. 2013; 17: R199
- Hyperbaric oxygen therapy palliates lipopolysaccharide-induced acute lung injury in rats by upregulating AQP1 and AQP5 expression.Exp Lung Res. 2015; 41: 444-449
- Amelioration of airway inflammation and pulmonary edema by Teucrium stocksianum via attenuation of pro-inflammatory cytokines and up-regulation of AQP1 and AQP5.Respir Physiol Neurobiol. 2021; 284103569
- The role of proinflammatory cytokines in lung ischemia-reperfusion injury.J Thorac Cardiovasc Surg. 2003; 125: 261-272
- Cytokine profile after lung transplantation: correlation with allograft injury.Ann Thorac Surg. 2006; 81 (discussion 49-50): 1844-1849
- Impact of cytokine expression in the pre-implanted donor lung on the development of chronic lung allograft dysfunction subtypes.Am J Transplant. 2013; 13: 3192-3201
- MEF2C alleviates acute lung injury in cecal ligation and puncture (CLP)-induced sepsis rats by up-regulating AQP1.Allergol Immunopathol (Madr). 2021; 49: 117-124
- Altered ubiquitination and stability of aquaporin-1 in hypertonic stress.Proc Natl Acad Sci USA. 2001; 98: 2894-2898
- Aquaporin-1 translocation and degradation mediates the water transportation mechanism of acetazolamide.Plos One. 2012; 7: e45976
- Acetazolamide reversibly inhibits water conduction by aquaporin-4.J Struct Biol. 2009; 166: 16-21
- Acetazolamide alleviate cerebral edema induced by ischemic stroke through inhibiting the expression of AQP4 mRNA.Neurocrit Care. 2022; 36: 97-105
- Kidney-lung cross-talk and acute kidney injury.Pediatr Nephrol. 2013; 28: 2239-2248
- Aquaporin-1 translocation and degradation mediates the water transportation mechanism of acetazolamide.Plos One. 2012; 7: e45976
- Acetazolamide enhances the release of urinary exosomal aquaporin-1.Nephrol Dial Transplant. 2016; 31: 1623-1632
- Endothelial transient receptor potential V4 channels mediate lung ischemia-reperfusion injury.Ann Thorac Surg. 2022; 113: 1256-1264
Article info
Publication history
Published online: September 05, 2022
Accepted:
August 29,
2022
Received:
December 25,
2021
Identification
Copyright
© 2022 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.
