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

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



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.


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.


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.


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.


Laryngopharyngeal reflux Pepsin Chronic rhinosinusitis Heat shock protein 70 Mitogen-activated protein kinase 



This study was funded by the International Scientific and Technological Cooperation Projects of Sichuan Province (no. 2016HH0064); Fundamental Research Funds for the Central Universities (No. 2012017yjsy118).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflicts of interest.

Ethical approval

This article does not contain any studies with human participants or animals performed by any of the authors.

Informed consent



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© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Oto-Rhino-Laryngology, West China Medical School, West China HospitalSichuan UniversityChengduChina
  2. 2.School of Medical and Life SciencesChengdu University of Traditional Chinese MedicineChengduChina
  3. 3.Department of Biomedical ResearchNemours/Alfred I.duPont Hospital for ChildrenWilmingtonUSA

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