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Common gene expression patterns responsive to mild temperature hyperthermia in normal human fibroblastic cells
Yoshiaki Tabuchi1, Yukihiro Furusawa, Ayako Kariya
1Division of Molecular Genetics Research, Life Science Research Centre, University of Toyama, Japan. ytabu@cts.u-toyoma.ac.jp
Summary
Mild hyperthermia (MHT) triggers significant gene expression changes in normal human fibroblasts (NHF) cells. These changes reveal molecular networks involved in endoplasmic reticulum stress and cell survival pathways.
Area of Science:
- Cellular Biology
- Molecular Biology
- Genomics
Background:
- Heat stress elicits complex cellular responses.
- The precise molecular mechanisms of heat stress, particularly mild hyperthermia (MHT), require further elucidation.
- Understanding these mechanisms is crucial for cellular protection and therapeutic strategies.
Purpose of the Study:
- To investigate the molecular mechanisms of cellular responses to mild hyperthermia (MHT) in normal human fibroblastic (NHF) cells.
- To identify genes and gene networks involved in the cellular response to MHT.
- To provide a molecular basis for understanding MHT response pathways.
Main Methods:
- Normal human fibroblastic (NHF) cell lines (Hs68 and OUMS-36) were exposed to MHT (41°C for 30 minutes).
- Gene expression profiling was performed using the GeneChip® system.
- Bioinformatics tools, including k-means clustering and gene network analysis, were employed.
Main Results:
- MHT treatment did not impact NHF cell viability or cell cycle progression.
- A significant number of probe sets (>1.5-fold change) were differentially expressed post-MHT.
- K-means clustering identified three gene clusters (Up-I, Down-I, Down-II).
- Two distinct gene networks were identified from up-regulated genes in cluster Up-I, associated with endoplasmic reticulum stress (DDIT3, HSPA5) and cell survival (HBEGF, LIF).
- Microarray findings were validated by quantitative real-time polymerase chain reaction in four NHF cell types.
Conclusions:
- Common differentially expressed genes and gene networks in response to MHT in NHF cells were identified.
- The study identified specific molecular pathways, including endoplasmic reticulum stress and cell survival, activated by MHT.
- These findings contribute to a deeper understanding of the molecular basis underlying cellular responses to mild hyperthermia.
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