Heat Shock Protein-70 Levels Are Associated With a State of Oxidative Damage in the Development of Bronchopulmonary Dysplasia

Chien-Chou Hsiao; Cheng-Han Lee; Rei-Cheng Yang; Jia-Yuh Chen; Tzu-Cheng Su; Yu-Jun Chang; Ching-Yuang Lin; Yi-Giien Tsai

doi:10.3389/fped.2021.616452

Heat Shock Protein-70 Levels Are Associated With a State of Oxidative Damage in the Development of Bronchopulmonary Dysplasia

Front Pediatr. 2021 May 26:9:616452. doi: 10.3389/fped.2021.616452. eCollection 2021.

Authors

Chien-Chou Hsiao^{1

2

3}, Cheng-Han Lee¹, Rei-Cheng Yang^{2

4}, Jia-Yuh Chen¹, Tzu-Cheng Su⁵, Yu-Jun Chang⁶, Ching-Yuang Lin⁷, Yi-Giien Tsai^{1

2

3}

Affiliations

¹ Department of Pediatrics, Changhua Christian Children's Hospital, Changhua, Taiwan.
² School of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
³ School of Medicine, Chung Shan Medical University, Taichung, Taiwan.
⁴ Department of Pediatrics, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
⁵ Department of Pathology, Changhua Christian Hospital, Changhua, Taiwan.
⁶ Epidemiology and Biostatistics and Big Data Center, Changhua Christian Hospital, Changhua, Taiwan.
⁷ Division of Pediatric Nephrology, Children's Hospital, China Medical University, Taichung, Taiwan.

Abstract

Background: Heat shock protein-70 (Hsp-70) exhibits cytoprotective effects against oxidative stress-induced airway injury. This study aimed to examine Hsp-70 and 8-hydroxy-2'-deoxyguanosine (8-OHdG) from tracheal aspirates (TA) in very low-birth weight (VLBW) preterm infants to predict the development of bronchopulmonary dysplasia (BPD). Methods: This birth cohort study enrolled 109 VLBW preterm infants, including 32 infants who developed BPD. Hsp-70 and 8-OHdG concentrations from TA were measured by immunoassay. The apoptosis of TA epithelial cells obtained on Day 28 after birth was measured using annexin-V staining assay. Results: Hsp-70 and 8-OHdG levels in TA fluid were persistently increased from Day 1 to Day 28 of life in the BPD group. Multiple linear regression analysis demonstrated that BPD was significantly associated with gestational age, respiratory distress syndrome, and TA Hsp-70 and 8-OHdG levels on post-natal Day 28. The TA Hsp-70 level positively correlated with TA 8-OHdG level on the Day 1 (r = 0.47) and Day 28 of life (r = 0.68). Incubation of recombinant Hsp-70 with primary epithelial cells derived from TA of patients decreased hydrogen peroxide-induced epithelial cell death. Conclusions: Hsp-70 levels are associated with a state of oxidative injury in the development of BPD.

Keywords: apoptosis; bronchopulmonary dysplasia; heat shock protein-70; oxidative stress; preterm infants.