2. Academic Validation
  3. Endoplasmic reticulum chaperone GRP78 participates in fluoride-induced autophagy in LS8 cells by regulating the IRE1-TRAF2-JNK pathway

Endoplasmic reticulum chaperone GRP78 participates in fluoride-induced autophagy in LS8 cells by regulating the IRE1-TRAF2-JNK pathway

  • Environ Toxicol. 2023 Apr 18. doi: 10.1002/tox.23805.
Lin Zhao 1 2,  Liyuan Wang 1 2 3,  Han Wang 1 2,  Tao Xi 1 2,  Sijia Liu 1 2,  Yang Li 1 2,  Jianping Ruan 4 5,  Yongqing Huang 1 2 3
Affiliations

Affiliations

  • 1 College of Stomatology, Ningxia Medical University, Yinchuan, China.
  • 2 Ningxia Key Laboratory of Cranio-maxillofacial Deformities, Ningxia Medical University, Yinchuan, China.
  • 3 Stomatological Hospital of General Hospital of Ningxia Medical University, Yinchuan, China.
  • 4 Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, College of Stomatology, Xi'an Jiaotong University, Xi'an, China.
  • 5 Clinical Research Center of Shaanxi Province for Dental and Maxillofacial Diseases, Center of Oral Public Health, College of Stomatology, Xi'an Jiaotong University, Xi'an, China.
PMID: 37070943 DOI: 10.1002/tox.23805
Abstract

Fluoride induces endoplasmic reticulum (ER) stress in ameloblasts, which is responsible for enamel mineralization disorder. Fluoride induces Autophagy in ameloblasts, but the molecular mechanisms through which ameloblasts respond to fluoride-induced cellular stress and Autophagy remain unclear. This study investigated ER stress-induced Autophagy and the regulatory role of the ER molecular chaperone GRP78 in fluoride-induced Autophagy in ameloblast LS8 cells. To explore the relationship between fluoride-induced ER stress and Autophagy, we assessed changes in fluoride-induced Autophagy in LS8 cells following overexpression and/or silencing of the ER stress molecular chaperone GRP78. We found that Autophagy induced by fluoride was further increased after GRP78 overexpression in LS8 cells. Fluoride-induced Autophagy was reduced in GRP78-silenced LS8 cells. Furthermore, we found that ER stress can regulate Autophagy in fluoride-treated ameloblasts (LS8 cells) and that the GRP78/IRE1/TRAF2/JNK pathway is involved in the underlying regulation. Our study suggests that ER stress plays a role in fluoride-induced damage by inducing ameloblast Autophagy.

Keywords

GRP78; LS8; NaF; autophagy; endoplasmic reticulum stress.

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