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J. Yu et al. / Comparative Biochemistry and Physiology, Part A xxx (2010) xxx–xxx
Mitogen-activated protein kinase (MAPK) signaling pathways are important downstream targets of activated growth factor receptors (such as EGFR and PDGFR) involved in mediating the intracellular response to extracellular stimuli. In mammals, three primary MAPKs exist including extracellular signal-regulated protein kinase (ERK), c-Jun NH2-terminal kinase (JNK), and p38 MAPK (Anderson, 2006). MAPKs are activated in response to extracellular stresses including UV radiation, osmotic shock, heat shock and lipopolysaccharides, in addition to activation by endogenous factors including growth cytokines, autacoids and neurotransmitters (Muthusamy and Piva, 2010). MAPK signaling regulates a wide range of intracellular activity, including gene expression, cell differentiation, cell proliferation, cell survival and apoptosis (Sompallae et al., 2008). We previously reported that heat stress signiﬁcantly injured the pig small intestine epithelial tissue, and this tissue was rapidly repaired within a few days. Based on our gene expression analysis, we suggest that heat stress-induced alterations in MAPK signaling may regulate the repair and regeneration of the damaged intestinal epithelium by encouraging crypt cell proliferation and migration. In conclusion, the present study investigated the effect of heat stress on morphology and gene expression in the porcine small intestine. Heat stress was found to cause signiﬁcant morphological damage to the epithelium of the pig small intestine. Gene expression proﬁling analysis revealed 203 genes to be differentially expressed in response to heat stress. Subsequent bioinformatic analysis of the differentially expressed genes provides signiﬁcant insight into the potential mechanisms underlying heat stress-induced damage as well as repair/regeneration in porcine small intestines. Acknowledgments We are thankful for the help from the members of CAU-BUA TCVM teaching and research team. This work was supported by grants from the National Natural Science Foundation of China (No. 30771566), the Beijing Education Committee Programs of Academic Innovation Team, Beijing Natural Science Foundation (No. 6082007) and the National Eleventh Five-Year Scientiﬁc and Technological Support Plan (No. 2008BADB4B01, 2008BADB4B07). References Anderson, D.H., 2006. Role of lipids in the MAPK signaling pathway. Prog. Lipid Res. 45, 102–119. Cario, E., Gerken, G., Podolsky, D.K., 2002. "For whom the bell tolls!" — innate defense mechanisms and survival strategies of the intestinal epithelium against lumenal pathogens. Z. Gastroenterol. 40, 983–990. Elez, D., Vidovic, S., Matic, G., 2000. The inﬂuence of hyperthermic stress on the redox state of glucocorticoid receptor. Stress 3, 247–255. Gisolﬁ, C.V., 2000. Is the GI system built for exercise? News Physiol. Sci. 15, 114–119. Hahn, J.S., Hu, Z., Thiele, D.J., Iyer, V.R., 2004. Genome-wide analysis of the biology of stress responses through heat shock transcription factor. Mol. Cell. Biol. 24, 5249–5256. Hall, D.M., Buettner, G.R., Oberley, L.W., Xu, L., Matthes, R.D., Gisolﬁ, C.V., 2001. Mechanisms of circulatory and intestinal barrier dysfunction during whole body hyperthermia. Am. J. Physiol. 280, H509–H521.
Hardy, J.D., Soderstrom, G.F., 1938. Heat loss from the nude body and peripheral blood ﬂow at temperatures of 22 °C to 35 °C: two ﬁgures. J. Nutr. 16, 493–510. Heise, K., Puntarulo, S., Pörtner, H.O., Abele, D., 2003. Production of reactive oxygen species by isolated mitochondria of the Antarctic bivalve Laternula elliptica (King and Broderip) under heat stress. Comp. Biochem. Physiol. C Toxicol. Pharmacol. 134, 79–90. Hirata, Y., Broquet, A.H., Menchen, L., Kagnoff, M.F., 2007. Activation of innate immune defense mechanisms by signaling through RIG-I/IPS-1 in intestinal epithelial cells. J. Immunol. 179, 5425–5432. Hua, G., Zhang, Q., Fan, Z., 2007. Heat shock protein 75 (TRAP1) antagonizes reactive oxygen species generation and protects cells from granzyme M-mediated apoptosis. J. Biol. Chem. 282, 20553–20560. Hui, R., Kameda, H., Risinger, J.I., Angerman-Stewart, J., Han, B., Barrett, J.C., Eling, T.E., Glasgow, W.C., 1999. The linoleic acid metabolite, 13-HpODE augments the phosphorylation of EGF receptor and SHP-2 leading to their increased association. Prostaglandins Leukot. Essent. Fatty Acids 61, 137–143. Kaushik, S., Kaur, J., 2005. Effect of chronic cold stress on intestinal epithelial cell proliferation and inﬂammation in rats. Stress 8, 191–197. Kawajiri, H., Hsi, L.C., Kamitani, H., Ikawa, H., Geller, M., Ward, T., Eling, T.E., Glasgow, W.C., 2002. Arachidonic and linoleic acid metabolism in mouse intestinal tissue: evidence for novel lipoxygenase activity. Arch. Biochem. Biophys. 398, 51–60. Keller, J.M., Escara-Wilke, J.F., Keller, E.T., 2008. Heat stress-induced heat shock protein 70 expression is dependent on ERK activation in zebraﬁsh (Danio rerio) cells. Comp. Biochem. Physiol. A Mol. Integr. Physiol. 150, 307–314. Kregel, K.C., Wall, P.T., Gisolﬁ, C.V., 1988. Peripheral vascular responses to hyperthermia in the rat. J. Appl. Physiol. 64, 2582–2588. Kültz, D., 2005. Molecular and evolutionary basis of the cellular stress response. Annu. Rev. Physiol. 67, 225–257. Leon, L.R., DuBose, D.A., Mason, C.W., 2005. Heat stress induces a biphasic thermoregulatory response in mice. Am. J. Physiol. 288, R197–R204. Liu, F., Yin, J., Du, M., Yan, P., Xu, J., Zhu, X., Yu, J., 2009. Heat-stress-induced damage to porcine small intestinal epithelium associated with downregulation of epithelial growth factor signaling. J. Anim. Sci. 87, 1941–1949. Mahmoud, K.Z., Edens, F.W., Eisen, E.J., Havenstein, G.B., 2004. Ascorbic acid decreases heat shock protein 70 and plasma corticosterone response in broilers (Gallus gallus domesticus) subjected to cyclic heat stress. Comp. Biochem. Physiol. B Biochem. Mol. Biol. 137, 35–42. Marai, I.F.M., El-Darawany, A.A., Fadiel, A., Abdel-Hafez, M.A.M., 2007. Physiological traits as affected by heat stress in sheep. A review. Small Rumin. Res. 71, 1–12. Muthusamy, V., Piva, T.J., 2010. The UV response of the skin: a review of the MAPK, NFkappaB and TNFalpha signal transduction pathways. Arch. Dermatol. Res. 302 (1), 5–17. Pace, T.W., Gaylord, R.I., Jarvis, E., Girotti, M., Spencer, R.L., 2008. Differential glucocorticoid effects on stress-induced gene expression in the paraventricular nucleus of the hypothalamus and ACTH secretion in the rat. Stress 12, 400–411. Rowell, L.B., 1974. Human cardiovascular adjustments to exercise and thermal stress. Physiol. Rev. 54, 75–159. Sinha, R.K., 2008. Serotonin synthesis inhibition by pre-treatment of p-CPA alters sleepelectrophysiology in an animal model of acute and chronic heat stress. J. Therm. Biol. 33, 261–273. Sompallae, R., Stavropoulou, V., Houde, M., Masucci, M.G., 2008. The MAPK Signaling Cascade is a central hub in the regulation of cell cycle, apoptosis and cytoskeleton remodeling by tripeptidyl-peptidase II. Gene Regul. Syst. Biol. 2, 253–265. Sonna, L.A., Fujita, J., Gafﬁn, S.L., Lilly, C.M., 2002. Invited review: effects of heat and cold stress on mammalian gene expression. J. Appl. Physiol. 92, 1725–1742. Srikandakumar, A., Johnson, E.H., Mahgoub, O., 2003. Effect of heat stress on respiratory rate, rectal temperature and blood chemistry in Omani and Australian Merino sheep. Small Rumin. Res. 49, 193–198. St-Pierre, N.R., Cobanov, B., Schnitkey, G., 2003. Economic losses from heat stress by US livestock industries. J. Dairy Sci. 86, E52–E77. Trevino, V., Falciani, F., Barrera-Saldana, H.A., 2007. DNA microarrays: a powerful genomic tool for biomedical and clinical research. Mol. Med. 13, 527–541. Young, J.T., Gauley, J., Heikkila, J.J., 2009. Simultaneous exposure of Xenopus A6 kidney epithelial cells to concurrent mild sodium arsenite and heat stress results in enhanced hsp30 and hsp70 gene expression and the acquisition of thermotolerance. Comp. Biochem. Physiol. A Mol. Integr. Physiol. 153 (433), 417–424. Zeldin, D.C., 2001. Epoxygenase pathways of arachidonic acid metabolism. J. Biol. Chem. 276, 36059–36062.
Please cite this article as: Yu, J., et al., Effect of heat stress on the porcine small intestine: A morphological and gene expression study, Comp. Biochem. Physiol. A (2010), doi:10.1016/j.cbpa.2010.01.008
Published on Apr 5, 2010
Published on Apr 5, 2010
Keywords: Heat stress Morphology Gene expression Electron microscope Microarray Small intestine Pig Article history: Received 26 November 20...