LRRK2 is involved in heat exposure-induced acute lung injury and alveolar type II epithelial cell dysfunction.

Abstract

Heat exposure induces excessive hyperthermia associated with systemic inflammatory response that leads to multiple organ dysfunction including acute lung injury. However, how heat impairs the lung remains elusive so far. We aimed to explore the underlying mechanism by focusing on leucine-rich repeat kinase 2 (LRRK2), which was associated with lung homeostasis. Both in vivo and in vitro models were induced by heat exposure. Firstly, heat exposure exerted core temperature (Tc) disturbance, pulmonary dysfunction, atelectasis, inflammation, impaired energy metabolism, and reduced surfactant proteins in the lung of mice. In addition, decreased LRRK2 expression and increased heat shock proteins (HSPs) 70 were observed with heat exposure in both the lung of mice and alveolar type II epithelial cells (AT2). Furthermore, LRRK2 inhibition aggravated heat exposure-initiated Tc dysregulation, injury in the lung and AT2 cells, and enhanced HSP70 expression. In conclusion, LRRK2 is involved in heat-induced acute lung injury and AT2 cell dysfunction.

• Authors: Yindan Wang, Wenjun Fan, Guoqing Zhang, Lisha Zhao, Ting Li, Lu Zhang, Tong Hou, Huihua Hong, Zhenqiang You, Qinghua Sun, Ran Li, Cuiqing Liu
• Journal: Environmental pollution (Barking, Essex : 1987) (Environ Pollut) Vol. 347 Pg. 123643 (Apr 15 2024) ISSN: 1873-6424 [Electronic] England
• PMID: 38428793 (Publication Type: Journal Article)
• Copyright: Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.

Chemical References

• LRRK2 protein, human
• Leucine-Rich Repeat Serine-Threonine Protein Kinase-2

Topics

• Humans
• Alveolar Epithelial Cells (metabolism)
• Lung
• Acute Lung Injury (chemically induced, metabolism)
• Lung Injury
• Leucine-Rich Repeat Serine-Threonine Protein Kinase-2 (genetics, metabolism)