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Published in: European Archives of Oto-Rhino-Laryngology 3/2019

01-03-2019 | Shock | Rhinology

Heat shock protein 70 is induced by pepsin via MAPK signaling in human nasal epithelial cells

Authors: Jing Wang, Yu Zhao, Jianjun Ren, Yang Xu, Wen Yang, Lei Lei, Yongbo Zheng, Zhang Qinxiu, Zhaoping He

Published in: European Archives of Oto-Rhino-Laryngology | Issue 3/2019

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Abstract

Background

Recent studies have shown that laryngopharyngeal reflux is associated with chronic rhinosinusitis. Pepsin may be a key factor involved in the injury of nasal mucosal epithelial cells, but the pathogenesis remains unclear. We are to investigate whether a mitogen-activated protein kinase (MAPK) pathway regulates heat shock protein 70 (HSP70) expression in primary cultures of human nasal epithelial cells (HNEpCs) in response to pepsin stimulation.

Methods

HSP70 protein expression levels in HNEpCs were estimated by Western blot analysis after treatment with pepsin. MAPK pathway activity levels were also evaluated to elucidate the mechanism underlying the effects of pepsin on HSP70 in HNEpCs. Inhibitors of signaling pathways were used to determine the contribution of MAPKs in HSP70 response after pepsin stimulation. Cellular apoptosis and cell viability in HNEpCs after treatment with pepsin were measured.

Results

The expression of HSP70 increased after stimulation with pepsin and decreased after the removal of pepsin. Pepsin induced activation of p38, extracellular signal-regulated kinase 1/2, and c-Jun N-terminal kinase (JNK) 1/2. Inhibition of JNK1/2 reduced HSP70 expression in HNEpCs. The apoptosis in HNEpCs at 12 h after treatment with pepsin at pH 7.0 increased significantly when compared with the control and pH 7.0 groups. Cell viability decreased following exposure to pepsin at pH 7.0.

Conclusion

Pepsin, even under neutral pH 7.0, increases the expression of HSP70 in HNEpCs by activating the JNK/MAPK signaling pathway. Increased HSP70 may be the protective mechanism when pepsin presents in the other parts of the body.
Literature
1.
go back to reference Hastan D, Fokkens WJ, Bachert C, Newson RB, Bislimovska J, Bockelbrink A, Bousquet PJ, Brozek G, Bruno A, Dahlén SE, Forsberg B, Gunnbjörnsdóttir M, Kasper L, Krämer U, Kowalski ML, Lange B, Lundbäck B, Salagean E, Todo-Bom A, Tomassen P, Toskala E, van Drunen CM, Bousquet J, Zuberbier T, Jarvis D, Burney P (2011) Chronic rhinosinusitis in Europe—an underestimated disease. A GA2LEN study. Allergy 66(9):1216–1223CrossRefPubMed Hastan D, Fokkens WJ, Bachert C, Newson RB, Bislimovska J, Bockelbrink A, Bousquet PJ, Brozek G, Bruno A, Dahlén SE, Forsberg B, Gunnbjörnsdóttir M, Kasper L, Krämer U, Kowalski ML, Lange B, Lundbäck B, Salagean E, Todo-Bom A, Tomassen P, Toskala E, van Drunen CM, Bousquet J, Zuberbier T, Jarvis D, Burney P (2011) Chronic rhinosinusitis in Europe—an underestimated disease. A GA2LEN study. Allergy 66(9):1216–1223CrossRefPubMed
2.
go back to reference Dibaise JK, Sharma VK (2006) Does gastroesophageal reflux contribute to the development of chronic sinusitis? A review of the evidence. Dis Esophagus 19(6):419–424CrossRefPubMed Dibaise JK, Sharma VK (2006) Does gastroesophageal reflux contribute to the development of chronic sinusitis? A review of the evidence. Dis Esophagus 19(6):419–424CrossRefPubMed
3.
go back to reference Lin YH, Chang TS, Yao YC, Li YC (2015) Increased risk of chronic sinusitis in adults with gastroesophgeal reflux disease: a nationwide population-based cohort study. Medicine (Baltimore) 94(39):e1642CrossRef Lin YH, Chang TS, Yao YC, Li YC (2015) Increased risk of chronic sinusitis in adults with gastroesophgeal reflux disease: a nationwide population-based cohort study. Medicine (Baltimore) 94(39):e1642CrossRef
4.
go back to reference Sharma N, Agrawal A, Freeman J, Vela MF, Castell D (2008) An analysis of persistent symptoms in acid-suppressed patients undergoing impedance-pH monitoring. Clin Gastroenterol Hepatol 6(5):521–524CrossRefPubMed Sharma N, Agrawal A, Freeman J, Vela MF, Castell D (2008) An analysis of persistent symptoms in acid-suppressed patients undergoing impedance-pH monitoring. Clin Gastroenterol Hepatol 6(5):521–524CrossRefPubMed
5.
go back to reference Kawamura O, Aslam M, Rittmann T, Hofmann C, Shaker R (2004) Physical and pH properties of gastroesophagopharyngeal refluxate: a 24-hour simultaneous ambulatory impedance and pH monitoring study. Am J Gastroenterol 99(6):1000–1010CrossRefPubMed Kawamura O, Aslam M, Rittmann T, Hofmann C, Shaker R (2004) Physical and pH properties of gastroesophagopharyngeal refluxate: a 24-hour simultaneous ambulatory impedance and pH monitoring study. Am J Gastroenterol 99(6):1000–1010CrossRefPubMed
6.
go back to reference Bardhan KD, Strugala V, Dettmar PW (2012) Reflux revisited: advancing the role of pepsin. Int J Otolaryngol 2012:646901CrossRefPubMed Bardhan KD, Strugala V, Dettmar PW (2012) Reflux revisited: advancing the role of pepsin. Int J Otolaryngol 2012:646901CrossRefPubMed
7.
go back to reference Hartl FU, Hayer-Hartl M (2002) Molecular chaperones in the cytosol: from nascent chain to folded protein. Science 295(5561):1852–1858CrossRefPubMed Hartl FU, Hayer-Hartl M (2002) Molecular chaperones in the cytosol: from nascent chain to folded protein. Science 295(5561):1852–1858CrossRefPubMed
8.
go back to reference Dreiseidler M, Dick N, Höhfeld J (2012) Analysis of chaperone-assisted ubiquitylation. Methods Mol Biol 832(:473–487CrossRefPubMed Dreiseidler M, Dick N, Höhfeld J (2012) Analysis of chaperone-assisted ubiquitylation. Methods Mol Biol 832(:473–487CrossRefPubMed
9.
go back to reference Asea A, Kraeft SK, Kurt-Jones EA, Stevenson MA, Chen LB, Finberg RW, Koo GC, Calderwood SK (2000) HSP70 stimulates cytokine production through a CD14-dependant pathway, demonstrating its dual role as a chaperone and cytokine. Nat Med 6(4):435–442CrossRefPubMed Asea A, Kraeft SK, Kurt-Jones EA, Stevenson MA, Chen LB, Finberg RW, Koo GC, Calderwood SK (2000) HSP70 stimulates cytokine production through a CD14-dependant pathway, demonstrating its dual role as a chaperone and cytokine. Nat Med 6(4):435–442CrossRefPubMed
10.
go back to reference Seki T, Yoshino KI, Tanaka S, Dohi E, Onji T, Yamamoto K, Hide I, Paulson HL, Saito N, Sakai N (2012) Establishment of a novel fluorescence-based method to evaluate chaperone-mediated autophagy in a single neuron. PLoS One 7(2):e31232CrossRefPubMedPubMedCentral Seki T, Yoshino KI, Tanaka S, Dohi E, Onji T, Yamamoto K, Hide I, Paulson HL, Saito N, Sakai N (2012) Establishment of a novel fluorescence-based method to evaluate chaperone-mediated autophagy in a single neuron. PLoS One 7(2):e31232CrossRefPubMedPubMedCentral
11.
go back to reference Currie RW, Karmazyn M, Kloc M, Mailer K (1988) Heat-shock response is associated with enhanced postischemic ventricular recovery. Circ Res 63(3):543–549CrossRefPubMed Currie RW, Karmazyn M, Kloc M, Mailer K (1988) Heat-shock response is associated with enhanced postischemic ventricular recovery. Circ Res 63(3):543–549CrossRefPubMed
12.
go back to reference Sittler A, Lurz R, Lueder G, Priller J, Lehrach H, Hayer-Hartl MK, Hartl FU, Wanker EE (2001) Geldanamycin activates a heat shock response and inhibits huntingtin aggregation in a cell culture model of Huntington’s disease. Hum Mol Genet 10(12):1307–1315CrossRefPubMed Sittler A, Lurz R, Lueder G, Priller J, Lehrach H, Hayer-Hartl MK, Hartl FU, Wanker EE (2001) Geldanamycin activates a heat shock response and inhibits huntingtin aggregation in a cell culture model of Huntington’s disease. Hum Mol Genet 10(12):1307–1315CrossRefPubMed
13.
go back to reference Kürthy M, Mogyorósi T, Nagy K, Kukorelli T, Jednákovits A, Tálosi L, Bíró K (2002) Effect of BRX-220 against peripheral neuropathy and insulin resistance in diabetic rat models. Ann N Y Acad Sci 967:482–489CrossRefPubMed Kürthy M, Mogyorósi T, Nagy K, Kukorelli T, Jednákovits A, Tálosi L, Bíró K (2002) Effect of BRX-220 against peripheral neuropathy and insulin resistance in diabetic rat models. Ann N Y Acad Sci 967:482–489CrossRefPubMed
14.
go back to reference Lin D, Lin H, Xiong X (2014) Expression and role of BAG-1 in eosinophilic and non-eosinophilic chronic rhinosinusitis with nasal polyps. Inflammation 37(6):1912–1918CrossRefPubMed Lin D, Lin H, Xiong X (2014) Expression and role of BAG-1 in eosinophilic and non-eosinophilic chronic rhinosinusitis with nasal polyps. Inflammation 37(6):1912–1918CrossRefPubMed
15.
go back to reference Min HJ, Hong SC, Yang HS, Mun SK, Lee SY (2016) Expression of CAIII and Hsp70 Is increased the mucous membrane of the posterior commissure in laryngopharyngeal reflux disease. Yonsei Med J 57(2):469–474CrossRefPubMedPubMedCentral Min HJ, Hong SC, Yang HS, Mun SK, Lee SY (2016) Expression of CAIII and Hsp70 Is increased the mucous membrane of the posterior commissure in laryngopharyngeal reflux disease. Yonsei Med J 57(2):469–474CrossRefPubMedPubMedCentral
16.
go back to reference Wang J, Yu Z, Ren J, Xu Y, Zhang Y, Lei L, Zheng Y, Huang L, He Z (2017) Effects of pepsin A on heat shock protein 70 response in laryngopharyngeal reflux patients with chronic rhinosinusitis. Acta Otolaryngol 137(12):1253–1259CrossRefPubMed Wang J, Yu Z, Ren J, Xu Y, Zhang Y, Lei L, Zheng Y, Huang L, He Z (2017) Effects of pepsin A on heat shock protein 70 response in laryngopharyngeal reflux patients with chronic rhinosinusitis. Acta Otolaryngol 137(12):1253–1259CrossRefPubMed
17.
go back to reference Widmann C, Gibson S, Jarpe MB, Johnson GL (1999) Mitogen-activated protein kinase: conservation of a three-kinase module from yeast to human. Physiol Rev 79(1):143–180CrossRefPubMed Widmann C, Gibson S, Jarpe MB, Johnson GL (1999) Mitogen-activated protein kinase: conservation of a three-kinase module from yeast to human. Physiol Rev 79(1):143–180CrossRefPubMed
18.
go back to reference Rubinfeld H, Seger R (2005) The ERK cascade: a prototype of MAPK signaling. Mol Biotechnol 31(2):151–174CrossRefPubMed Rubinfeld H, Seger R (2005) The ERK cascade: a prototype of MAPK signaling. Mol Biotechnol 31(2):151–174CrossRefPubMed
19.
go back to reference Bogoyevitch MA, Ngoei KR, Zhao TT, Yeap YY, Ng DC (2010) c-Jun N-terminal kinase (JNK) signaling: recent advances and challenges. Biochim Biophys Acta 1804(3):463–475CrossRefPubMed Bogoyevitch MA, Ngoei KR, Zhao TT, Yeap YY, Ng DC (2010) c-Jun N-terminal kinase (JNK) signaling: recent advances and challenges. Biochim Biophys Acta 1804(3):463–475CrossRefPubMed
20.
go back to reference Kyriakis JM, Avruch J (2012) Mammalian MAPK signal transduction pathways activated by stress and inflammation: a 10-year update. Physiol Rev 92(2):689–737CrossRefPubMed Kyriakis JM, Avruch J (2012) Mammalian MAPK signal transduction pathways activated by stress and inflammation: a 10-year update. Physiol Rev 92(2):689–737CrossRefPubMed
21.
go back to reference Naor Z, Benard O, Seger R (2000) Activation of MAPK cascades by G-protein-coupled receptors: the case of gonadotropin-releasing hormone receptor. Trends Endocrinol Metab 11(3):91–99CrossRefPubMed Naor Z, Benard O, Seger R (2000) Activation of MAPK cascades by G-protein-coupled receptors: the case of gonadotropin-releasing hormone receptor. Trends Endocrinol Metab 11(3):91–99CrossRefPubMed
22.
go back to reference Rangarajan A, Hong SJ, Gifford A, Weinberg RA (2004) Species- and cell type-specific requirements for cellular transformation. Cancer Cell 6(2):171–183CrossRefPubMed Rangarajan A, Hong SJ, Gifford A, Weinberg RA (2004) Species- and cell type-specific requirements for cellular transformation. Cancer Cell 6(2):171–183CrossRefPubMed
23.
go back to reference Volloch V, Gabai VL, Rits S, Force T, Sherman MY (2000) HSP72 can protect cells from heat-induced apoptosis by accelerating the inactivation of stress kinase JNK. Cell Stress Chaperones 5(2):139–147CrossRefPubMedPubMedCentral Volloch V, Gabai VL, Rits S, Force T, Sherman MY (2000) HSP72 can protect cells from heat-induced apoptosis by accelerating the inactivation of stress kinase JNK. Cell Stress Chaperones 5(2):139–147CrossRefPubMedPubMedCentral
24.
go back to reference Takeda K, Matsuzawa A, Nishitoh H, Tobiume K, Kishida S, Ninomiya-Tsuji J, Matsumoto K, Ichijo H (2004) Involvement of ASK1 in Ca2+-induced p38 MAP kinase activation. EMBO Rep 5(2):161–166CrossRefPubMedPubMedCentral Takeda K, Matsuzawa A, Nishitoh H, Tobiume K, Kishida S, Ninomiya-Tsuji J, Matsumoto K, Ichijo H (2004) Involvement of ASK1 in Ca2+-induced p38 MAP kinase activation. EMBO Rep 5(2):161–166CrossRefPubMedPubMedCentral
25.
go back to reference Matsuzawa A, Saegusa K, Noguchi T, Sadamitsu C, Nishitoh H, Nagai S, Koyasu S, Matsumoto K, Takeda K, Ichijo H (2005) ROS-dependent activation of the TRAF6-ASK1-p38 pathway is selectively required for TLR4-mediated innate immunity. Nat Immunol 6(6):587–592CrossRefPubMed Matsuzawa A, Saegusa K, Noguchi T, Sadamitsu C, Nishitoh H, Nagai S, Koyasu S, Matsumoto K, Takeda K, Ichijo H (2005) ROS-dependent activation of the TRAF6-ASK1-p38 pathway is selectively required for TLR4-mediated innate immunity. Nat Immunol 6(6):587–592CrossRefPubMed
26.
go back to reference Rafiee P, Theriot ME, Nelson VM, Heidemann J, Kanaa Y, Horowitz SA, Rogaczewski A, Johnson CP, Ali I, Shaker R, Binion DG (2006) Human esophageal microvascular endothelial cells respond to acidic pH stress by PI3K/AKT and p38 MAPK-regulated induction of Hsp70 and Hsp27. Am J Physiol Cell Physiol 291(5):C931–C945CrossRefPubMed Rafiee P, Theriot ME, Nelson VM, Heidemann J, Kanaa Y, Horowitz SA, Rogaczewski A, Johnson CP, Ali I, Shaker R, Binion DG (2006) Human esophageal microvascular endothelial cells respond to acidic pH stress by PI3K/AKT and p38 MAPK-regulated induction of Hsp70 and Hsp27. Am J Physiol Cell Physiol 291(5):C931–C945CrossRefPubMed
27.
go back to reference Bironaite D, Brunk U, Venalis A (2013) Protective induction of Hsp70 in heat-stressed primary myoblasts: Involvement of MAPKs. J Cell Biochem 114(9):2024–2031CrossRefPubMed Bironaite D, Brunk U, Venalis A (2013) Protective induction of Hsp70 in heat-stressed primary myoblasts: Involvement of MAPKs. J Cell Biochem 114(9):2024–2031CrossRefPubMed
28.
go back to reference Johnston N, Dettmar PW, Bishwokarma B, Lively MO, Koufman JA (2007) Activity/stability of human pepsin: implications for reflux attributed laryngeal disease. Laryngoscope 117(6):1036–1039CrossRefPubMed Johnston N, Dettmar PW, Bishwokarma B, Lively MO, Koufman JA (2007) Activity/stability of human pepsin: implications for reflux attributed laryngeal disease. Laryngoscope 117(6):1036–1039CrossRefPubMed
29.
go back to reference Adhami T, Goldblum JR, Richter JE, Vaezi MF (2004) The role of gastric and duodenal agents in laryngeal injury: an experimental canine model. Am J Gastroenterol 99(11):2098–2106CrossRefPubMed Adhami T, Goldblum JR, Richter JE, Vaezi MF (2004) The role of gastric and duodenal agents in laryngeal injury: an experimental canine model. Am J Gastroenterol 99(11):2098–2106CrossRefPubMed
30.
go back to reference Johnston N, Wells CW, Blumin JH, Toohill RJ, Merati AL (2007) Receptor-mediated uptake of pepsin by laryngeal epithelial cells. Ann Otol Rhinol Laryngol 116(12):934–938CrossRefPubMed Johnston N, Wells CW, Blumin JH, Toohill RJ, Merati AL (2007) Receptor-mediated uptake of pepsin by laryngeal epithelial cells. Ann Otol Rhinol Laryngol 116(12):934–938CrossRefPubMed
31.
go back to reference Johnston N, Dettmar PW, Lively MO, Postma GN, Belafsky PC, Birchall M, Koufman JA (2006) Effect of pepsin on laryngeal stress protein (Sep70, Sep53, and Hsp70) response: role in laryngopharyngeal reflux disease. Ann Otol Rhinol Laryngol 115(1):47–58CrossRefPubMed Johnston N, Dettmar PW, Lively MO, Postma GN, Belafsky PC, Birchall M, Koufman JA (2006) Effect of pepsin on laryngeal stress protein (Sep70, Sep53, and Hsp70) response: role in laryngopharyngeal reflux disease. Ann Otol Rhinol Laryngol 115(1):47–58CrossRefPubMed
32.
go back to reference Washington N, Steele RJ, Jackson SJ, Bush D, Mason J, Gill DA, Pitt K, Rawlins DA (2000) Determination of baseline human nasal pH and the effect of intranasally administered buffers. Int J Pharm 198(2):139–146CrossRefPubMed Washington N, Steele RJ, Jackson SJ, Bush D, Mason J, Gill DA, Pitt K, Rawlins DA (2000) Determination of baseline human nasal pH and the effect of intranasally administered buffers. Int J Pharm 198(2):139–146CrossRefPubMed
33.
go back to reference DelGaudio JM (2005) Direct nasopharyngeal reflux of gastric acid is a contributing factor in refractory chronic rhinosinusitis. Laryngoscope 115(6):946–957CrossRefPubMed DelGaudio JM (2005) Direct nasopharyngeal reflux of gastric acid is a contributing factor in refractory chronic rhinosinusitis. Laryngoscope 115(6):946–957CrossRefPubMed
34.
go back to reference Ang D, Liberek K, Skowyra D, Zylicz M, Georgopoulos C (1991) Biological role and regulation of the universally conserved heat shock proteins. J Biol Chem 266(36):24233–24236PubMed Ang D, Liberek K, Skowyra D, Zylicz M, Georgopoulos C (1991) Biological role and regulation of the universally conserved heat shock proteins. J Biol Chem 266(36):24233–24236PubMed
35.
go back to reference Benjamin IJ, McMillan DR (1998) Stress (heat shock) proteins: molecular chaperones in cardiovascular biology and disease. Circ Res 83(2):117–132CrossRefPubMed Benjamin IJ, McMillan DR (1998) Stress (heat shock) proteins: molecular chaperones in cardiovascular biology and disease. Circ Res 83(2):117–132CrossRefPubMed
36.
go back to reference Amrani M, Corbett J, Allen NJ, O’Shea J, Boateng SY, May AJ, Dunn MJ, Yacoub MH (1994) Induction of heat-shock proteins enhances myocardial and endothelial functional recovery after prolonged cardioplegic arrest. Ann Thorac Surg 57(1):157–160CrossRefPubMed Amrani M, Corbett J, Allen NJ, O’Shea J, Boateng SY, May AJ, Dunn MJ, Yacoub MH (1994) Induction of heat-shock proteins enhances myocardial and endothelial functional recovery after prolonged cardioplegic arrest. Ann Thorac Surg 57(1):157–160CrossRefPubMed
37.
go back to reference Kukreja RC, Qian YZ, Okubo S, Flaherty EE (1999) Role of protein kinase C and 72 kDa heat shock protein in ischemic tolerance following heat stress in the rat heart. Mol Cell Biochem 195(1–2):123–131CrossRefPubMed Kukreja RC, Qian YZ, Okubo S, Flaherty EE (1999) Role of protein kinase C and 72 kDa heat shock protein in ischemic tolerance following heat stress in the rat heart. Mol Cell Biochem 195(1–2):123–131CrossRefPubMed
38.
go back to reference Kabakov AE, Budagova KR, Bryantsev AL, Latchman DS (2003) Heat shock protein 70 or heat shock protein 27 overexpressed in human endothelial cells during posthypoxic reoxygenation can protect from delayed apoptosis. Cell Stress Chaperones 8(4):335–347CrossRefPubMedPubMedCentral Kabakov AE, Budagova KR, Bryantsev AL, Latchman DS (2003) Heat shock protein 70 or heat shock protein 27 overexpressed in human endothelial cells during posthypoxic reoxygenation can protect from delayed apoptosis. Cell Stress Chaperones 8(4):335–347CrossRefPubMedPubMedCentral
39.
go back to reference Jäättelä M, Saksela K, Saksela E (1989) Heat shock protects WEHI-164 target cells from the cytolysis by tumor necrosis factors alpha and beta. Eur J Immunol 19(8):1413–1417CrossRefPubMed Jäättelä M, Saksela K, Saksela E (1989) Heat shock protects WEHI-164 target cells from the cytolysis by tumor necrosis factors alpha and beta. Eur J Immunol 19(8):1413–1417CrossRefPubMed
40.
go back to reference Larrick JW, Wright SC (1990) Cytotoxic mechanism of tumor necrosis factor-alpha. FASEB J 4(14):3215–3223CrossRefPubMed Larrick JW, Wright SC (1990) Cytotoxic mechanism of tumor necrosis factor-alpha. FASEB J 4(14):3215–3223CrossRefPubMed
41.
go back to reference Margulis BA, Sandler S, Eizirik DL, Welsh N, Welsh M (1991) Liposomal delivery of purified heat shock protein hsp70 into rat pancreatic islets as protection against interleukin 1 beta-induced impaired beta-cell function. Diabetes 40(11):1418–1422CrossRefPubMed Margulis BA, Sandler S, Eizirik DL, Welsh N, Welsh M (1991) Liposomal delivery of purified heat shock protein hsp70 into rat pancreatic islets as protection against interleukin 1 beta-induced impaired beta-cell function. Diabetes 40(11):1418–1422CrossRefPubMed
42.
go back to reference Zhang HY, Zhang X, Chen X, Thomas D, Hormi-Carver K, Elder F, Spechler SJ, Souza RF (2008) Differences in activity and phosphorylation of MAPK enzymes in esophageal squamous cells of GERD patients with and without Barrett’s esophagus. Am J Physiol Gastrointest Liver Physiol 295(3):G470–G478CrossRefPubMedPubMedCentral Zhang HY, Zhang X, Chen X, Thomas D, Hormi-Carver K, Elder F, Spechler SJ, Souza RF (2008) Differences in activity and phosphorylation of MAPK enzymes in esophageal squamous cells of GERD patients with and without Barrett’s esophagus. Am J Physiol Gastrointest Liver Physiol 295(3):G470–G478CrossRefPubMedPubMedCentral
43.
go back to reference Zhang L, Liu G, Han X, Liu J, Li GX, Zou DW, Li ZS (2015) Inhibition of p38 MAPK activation attenuates esophageal mucosal damage in a chronic model of reflux esophagitis. Neurogastroenterol Motil 27(11):1648–1656CrossRefPubMed Zhang L, Liu G, Han X, Liu J, Li GX, Zou DW, Li ZS (2015) Inhibition of p38 MAPK activation attenuates esophageal mucosal damage in a chronic model of reflux esophagitis. Neurogastroenterol Motil 27(11):1648–1656CrossRefPubMed
44.
go back to reference Uehara T, Kaneko M, Tanaka S, Okuma Y, Nomura Y (1999) Possible involvement of p38 MAP kinase in HSP70 expression induced by hypoxia in rat primary astrocytes. Brain Res 823(1–2):226–230CrossRefPubMed Uehara T, Kaneko M, Tanaka S, Okuma Y, Nomura Y (1999) Possible involvement of p38 MAP kinase in HSP70 expression induced by hypoxia in rat primary astrocytes. Brain Res 823(1–2):226–230CrossRefPubMed
45.
go back to reference Sheikh-Hamad D, Di MJ, Suki WN, Safirstein R, Watts BA, Rouse D (1998) p38 kinase activity is essential for osmotic induction of mRNAs for HSP70 and transporter for organic solute betaine in Madin-Darby canine kidney cells. J Biol Chem 273(3):1832–1837CrossRefPubMed Sheikh-Hamad D, Di MJ, Suki WN, Safirstein R, Watts BA, Rouse D (1998) p38 kinase activity is essential for osmotic induction of mRNAs for HSP70 and transporter for organic solute betaine in Madin-Darby canine kidney cells. J Biol Chem 273(3):1832–1837CrossRefPubMed
Metadata
Title
Heat shock protein 70 is induced by pepsin via MAPK signaling in human nasal epithelial cells
Authors
Jing Wang
Yu Zhao
Jianjun Ren
Yang Xu
Wen Yang
Lei Lei
Yongbo Zheng
Zhang Qinxiu
Zhaoping He
Publication date
01-03-2019
Publisher
Springer Berlin Heidelberg
Published in
European Archives of Oto-Rhino-Laryngology / Issue 3/2019
Print ISSN: 0937-4477
Electronic ISSN: 1434-4726
DOI
https://doi.org/10.1007/s00405-018-5254-3

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