title: Differential modulation of claudin 4 expression and myosin light chain phosphorylation by thyroid function in lung injury.
abstract: BACKGROUND
  Trauma and ventilator-induced lung injury is often associated with endothelial-epithelial barriers breakdown, which may lead to multiple system organ failure (MSOF) and death in critically ill patients. Although molecular mechanism involved in MSOF is not known, junctional opening is believed to happen. In vitro, thyroid hormones inhibit myosin light chain (MLC) phosphorylation and may, thus, inhibit cellular contraction and junctional opening. Trauma is also associated with tissue hypo-thyroid state. Therefore, we examined the effects of thyroid function on expression of phospho-MLC (pp-MLC) and claudin 4 (Clud4), key proteins involved in regulation of junctional tightness, in lung injury.
  
  
  METHODS
  Rats were rendered hypo-thyroid (Hypo) or hyperthyroid (Hyper) by adding methimazole or levo-thyroxine, respectively, to their drinking water. Untreated euthyroid (Eue) animals were used as control. Lung pp-MLC and Clud4 proteins were assessed by western blotting and in situ immunodetection, respectively. Lung injury was induced by high tidal volume mechanical ventilation.
  
  
  RESULTS
  Lung injury was significantly enhanced in Hypo animals and attenuated in Hyper animals. Parallel changes in expression of lung pp-MLC were detected. Alterations in lung histomorphology correlated with the level of pp-MLC. Expression of alveolar and bronchiolar Clud4 protein was differentially affected by the state of thyroid gland.
  
  
  CONCLUSIONS
  Our data suggest that thyroid function plays significant role in lung injury perhaps by modulating expression of the proteins involved in junctional tightness. Besides, they strongly support the idea that the tissue hypo-thyroid state may contribute to endothelial-epithelial barriers breakdown associated with trauma.
authors.affiliation: Department of Physiology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran.
authors.forename: Masoumeh
authors.initials: M
authors.lastname: Varedi
authors.affiliation: Department of Physiology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran.
authors.forename: Naser
authors.initials: N
authors.lastname: Pajouhi
authors.affiliation: Department of Pathology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Owji
authors.affiliation: Department of Biochemistry, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran.
authors.forename: Fakhraddin
authors.initials: F
authors.lastname: Naghibalhossaini
authors.affiliation: Department of Internal Medicine and Endocrine/Metabolism Research Center, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran.
authors.forename: Gholam H R
authors.initials: GHR
authors.lastname: Omrani
mesh_terms: D000818:Animals; D062506:Claudin-4; D016638:Critical Illness / Q000401:mortality; D004727:Endothelium / Q000293:injuries* / Q000473:pathology; D006801:Humans; D055370:Lung Injury / Q000378:metabolism* / Q000401:mortality / Q000473:pathology / Q000662:veterinary; D008297:Male; D023421:Models, Animal; D009102:Multiple Organ Failure / Q000209:etiology; D018994:Myosin Light Chains / Q000378:metabolism*; D010766:Phosphorylation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012121:Respiration, Artificial / Q000009:adverse effects / Q000706:statistics & numerical data; D013961:Thyroid Gland / Q000378:metabolism* / Q000502:physiology; D013963:Thyroid Hormones / Q000378:metabolism* / Q000502:physiology; D019108:Tight Junctions / Q000378:metabolism
chemical_list: D062506:Claudin-4; D018994:Myosin Light Chains; D013963:Thyroid Hormones
keywords: claudin; epithelial barrier; lung injury; myosin light chain; thyroid