Gene Array Analysis Reveals Consensus Heat Stress Response in Rat Liver, Lung, Heart, and Kidney

Heat stroke (HS) is characterized by severe hyperthermia and a systemic inflammatory response syndrome that often results in multi‐organ damage (MOD). To identify molecular mechanisms mediating MOD, we examined global gene expression in rat liver, heart, lung, and kidney at a core temperature of 41.8°C (Tc,Max), 24h, and 48h. The largest gene response was in the liver, which correlated with a computational model of heat distribution at Tc,Max. In all organs, HS induced a consensus response of 66 transcripts, which were functionally enriched with annotated heat shock, anti‐apoptosis, and inflammation genes. We identified Zfand2a, Slc5a3, and SNORD14, novel genes not previously associated with the in vivo HS response. Each organ also demonstrated a unique HS response, such as HS‐induced Crayb (HSP20), HMGB1‐like protein, and IL10 in liver, all known inflammatory mediators. Consensus and organ specific markers may be exploited to assess HS‐induced MOD and subsequent recovery. Research supported by MRMC. Research was conducted in compliance with the Animal Welfare Act, and all other Federal requirements. The views expressed are those of the authors and do not constitute endorsement by the US Army.