Differential modulation of claudin 4 expression and myosin light chain phosphorylation by thyroid function in lung injury.

Autor: Varedi M; Department of Physiology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran., Pajouhi N; Department of Physiology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran., Owji M; Department of Pathology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran., Naghibalhossaini F; Department of Biochemistry, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran., Omrani GHR; Department of Internal Medicine and Endocrine/Metabolism Research Center, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran.
Jazyk: angličtina
Zdroj: The clinical respiratory journal [Clin Respir J] 2017 Nov; Vol. 11 (6), pp. 797-804. Date of Electronic Publication: 2015 Dec 28.
DOI: 10.1111/crj.12418
Abstrakt: 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.
(© 2015 John Wiley & Sons Ltd.)
Databáze: MEDLINE
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