Expression of heme oxygenase-1 in type II pneumocytes protects against heatstroke-induced lung damage
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ORIGINAL PAPER
Expression of heme oxygenase-1 in type II pneumocytes protects against heatstroke-induced lung damage Chin-Kun Tseng 1,2 & Tsung-Ta Liu 3,4 & Tsung-Chieh Lin 5 & Chia-Pi Cheng 6 Received: 23 April 2020 / Revised: 5 August 2020 / Accepted: 10 August 2020 # Cell Stress Society International 2020
Abstract Heatstroke (HS) is an acute clinical disease characterized by abnormal hyperthermia and multi-organ dysfunction. Heme oxygenase (HO)-1, also called heat shock protein (HSP)32, is induced by hyperthermia and also plays protective roles in many lung disease models. Based on this phenomenon, we investigated the protective role of endogenous HO-1 in heatinduced lung damage in rats. Male Sprague-Dawley (SD) rats were separated into three groups: (a) normothermic sham, (b) HS, and (c) SnPP (inhibitor of HO-1) pretreatment rats. In the HS group, rats were killed at various time points (1, 3, 6, and 12 h after heat exposure) in order to analyze messenger ribonucleic acid (mRNA) and protein levels. Lung sections were examined for tissue damage and localization of HO-1 using immunofluorescence double labeling. We found that HS induced lung pathology (congested and thickened lung septa). The level of HO-1 mRNA was increased at 1 h, and the protein level peaked at 6 h after heat exposure. Pretreatment with SnPP (tin-protoporphyrin IX, 30 mg/kg, intraperitoneal injection for 1 h before heat exposure) aggravated the lung damage. Furthermore, we demonstrated HO-1 expression in lung type II pneumocytes. Our results suggest that endogenous HO-1 is protective against HS-induced lung damage. Induction of HO-1 may be a potential therapeutic strategy for treating heat-related diseases. Keywords Heatstroke . Heme oxygenase-1 . SnPP . Type II pneumocyte
Introduction
Chin-Kun Tseng and Tsung-Ta Liu contributed equally to this article and both qualify as first authors. * Chia-Pi Cheng [email protected] 1
Tri-Service General Hospital Songsang Branch, National Defense Medical Center, Taipei, Taiwan
2
Department Electronic Engineering, National Taipei University of Technology, Taipei, Taiwan
3
Department of Physiology and Biophysics, National Defense Medical Center, Taipei, Taiwan
4
Nursing Department, Center for General Education, Kang-Ning University, Tainan, Taiwan
5
Genomic Medicine Core Laboratory, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan
6
Department and Graduate Institute of Biology and Anatomy, National Defense Medical Center, No.161, Sec. 6, Min-Chuan E. Rd., Neihu, 114 Taipei, Taiwan
Heatstroke (HS) is a disease with high mortality, characterized by an elevated core body temperature (Tco) exceeding 40 °C, central nervous system (CNS) dysfunction (confusion, delirium, coma, or seizures), and multi-organ failure (including the respiratory, hepatic, enteric, and renal systems) (Wen et al. 2015; Bruchim et al. 2017; Lin et al. 2018). The most frequent organ failure during HS is the lung (morbidity rate, 85.7%) (Varghese et al. 2005), and many patients (> 60%) require ventilatory suppo
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