Exposure to febrile-range hyperthermia potentiates Wnt signalling and epithelial–mesenchymal transition gene expression in lung epithelium

Content Provider	Scilit
Author	Potla, Ratnakar Tulapurkar, Mohan E. Luzina, Irina G. Atamas, Sergei P. Singh, Ishwar S. Hasday, Jeffrey D.
Copyright Year	2017
Description	Journal: International Journal of Hyperthermia As environmental and body temperatures vary, lung epithelial cells experience temperatures significantly different from normal core temperature. Our previous studies in human lung epithelium showed that: (1) heat shock accelerates wound healing and activates profibrotic gene expression through heat shock factor-1 (HSF1); (2) HSF1 is activated at febrile temperatures (38°−41°C); and (3) hypothermia (32°C) activates and hyperthermia (39.5°C) reduces expression of a subset of miRNAs that target protein kinase Cα (PKCα) and enhance proliferation. We analyzed the effect of hypo- and hyperthermia exposure on Wnt signalling by exposing human small airway epithelial cells (SAECs) and HEK293T cells to 32°C, 37°C, or 39.5°C for 24h, then analyzing Wnt-3a-induced epithelial mesenchymal transition (EMT) gene expression by qRT-PCR and TOPFlash reporter plasmid activity. Effects of miRNA mimics and inhibitors and the HSF1 inhibitor, KNK437, were evaluated. Exposure to 39.5°C for 24h increased subsequent Wnt-3a-induced EMT gene expression in SAECs and Wnt-3a-induced TOPFlash activity in HEK293T cells. Increased Wnt responsiveness was associated with HSF1 activation and blocked by KNK437. Overexpressing temperature-responsive miRNAs mimics reduced Wnt responsiveness in 39.5°C-exposed HEK293T cells, but inhibitors of the same miRNAs failed to restore Wnt responsiveness in 32°C-exposed HEK293T cells. Wnt responsiveness, including expression of genes associated with EMT, increases after exposure to febrile-range temperature through an HSF1-dependent mechanism that is independent of previously identified temperature-dependent miRNAs. This process may be relevant to febrile fibrosing lung diseases, including the fibroproliferative phase of acute respiratory distress syndrome (ARDS) and exacerbations of idiopathic pulmonary fibrosis (IPF).
Related Links	https://www.tandfonline.com/doi/pdf/10.1080/02656736.2017.1316875?needAccess=true https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7328721/pdf
ISSN	02656736
e-ISSN	14645157
DOI	10.1080/02656736.2017.1316875
Journal	International Journal of Hyperthermia
Issue Number	1
Volume Number	34
Language	English
Publisher	Informa UK Limited
Publisher Date	2018-01-02
Access Restriction	Open
Subject Keyword	Journal: International Journal of Hyperthermia Hyperthermia Heat Shock Factor-1 Epithelial-mesenchymal Transition
Content Type	Text
Subject	Physiology Physiology (medical) Cancer Research Radiological and Ultrasound Technology