Archives of Toxicology

, Volume 92, Issue 4, pp 1421–1434 | Cite as

The role of unfolded protein response and ER-phagy in quantum dots-induced nephrotoxicity: an in vitro and in vivo study

  • Shengwei Jiang
  • Yuchun Lin
  • Huan Yao
  • Chuanli Yang
  • Liyin Zhang
  • Bing Luo
  • Zhao Lei
  • Liwei Cao
  • Naibo Lin
  • Xiangyang LiuEmail author
  • Zhongning LinEmail author
  • Chengyong HeEmail author
Toxicokinetics and Metabolism


Unfolded protein response (UPR) and endoplasmic reticulum (ER)-phagy are essential for cell homeostasis. Quantum dots (QDs), which have been widely used for biomedical applications, can accumulate in the kidney tissues and may cause renal dysfunction. However, the molecular mechanism of QDs-induced nephrotoxicity is still obscure. The present study was aimed to elucidate the role and mechanism of UPR and ER-phagy in QDs-induced nephrotoxicity. Herein, human embyronic kidney (HEK) cells were exposed to 15, 30, 45, and 60 nM cadmium telluride (CdTe)-QDs for 12 and 24 h. And CdTe-QDs (30–60 nM) inhibited the HEK cell viability. The clathrin-dependent endocytosis was determined as the main pathway of CdTe-QDs cellular uptake. Within cells, CdTe-QDs disrupted ER ultrastructure and induced UPR and FAM134B-dependent ER-phagy. Blocking UPR with inhibitors or siRNA rescued the FAM134B-dependent ER-phagy, which was triggered by CdTe-QDs. Moreover, suppression of UPR or FAM134B-dependent ER-phagy restored the cell vability. In vivo, mice were intravenously injected with 8 and 16 nmol/kg body weight CdTe-QDs for 24 h. Kidney was shown as one of highest distributed organs of CdTe-QDs, resulting in renal dysfunction, as well as UPR and FAM134B-dependent ER-phagy in it. Thus, for the first time, we demonstrated that ER-phagy can be triggered by nanomaterials both in vitro and in vivo. In addition, blocking of UPR and ER-phagy showed protective effects against CdTe-QDs-induced toxicity in kideny cells. Notably, a secreted alkaline phosphatase reporter gene system has been developed as a sensitive and rapid method for evaluating the ER quality under the exposure of nanomaterials.


Quantum dots Unfolded protein response ER-phagy Endoplasmic reticulum quality control Autophagy FAM134B Kidney 





Blood urea nitrogen


Cell counting kit 8


Cadmium telluride


Ceric oxide








Cytochalasin D






Eukaryotic initiation factor 2 α-subunit


Endoplasmic reticulum


ER-associated protein degradation


ER quality control


The reticulon family with sequence similarity 134


Firefly luciferase


γ-aminobutyric acid receptor-associated protein


Glucose-regulated protein 78


Hematoxylin and eosin


High-resolution transmission electron microscopy


Microtubules-associated protein 1-light chain 3


Lactate dehydrogenase


Mercaptopropionic acid






Sodium hydrogen tellurium


Sodium borohydride




Optical density


PKR-like endoplasmic reticulum kinase


Quantum dots


Quantitative real-time PCR


Secreted alkaline phosphatase




Transmission electron microscopy




Titanium dioxide


Tauroursodeoxycholic acid


Uric acid


Unfolded protein response


Zinc oxide



We appreciate Dr. Lei Guo and Dr. Si Chen (National Center for Toxicological Research, USA) for their kind gift of plasmids related to SEAP reporter system. We appreciate Chao Song (Freshwater Fisheries Research Centre of Chinese Academy of Fishery Sciences) for help with AAS technique. We are grateful to Dr. Vitali Stanevich (R&D department, Janssen, USA), and Dr. Feng Guo (University of Wisconsin, USA) for editing the language. This work was supported by grants from the National Natural Science Foundation of China (NSFC Nos. 81402648, 81573181, 81472997, 81773465), the Natural Science Foundation of Fujian Province of China (No. 2015J01344), the Scientific Research Foundation of State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics (No. 2016ZY003), and the 1000 Talents Program from Xiamen University.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no competing interests.

Supplementary material

204_2018_2169_MOESM1_ESM.doc (555 kb)
Supplementary material 1 (DOC 555 KB)


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Shengwei Jiang
    • 1
  • Yuchun Lin
    • 1
  • Huan Yao
    • 1
  • Chuanli Yang
    • 1
  • Liyin Zhang
    • 1
  • Bing Luo
    • 1
  • Zhao Lei
    • 1
  • Liwei Cao
    • 2
  • Naibo Lin
    • 2
  • Xiangyang Liu
    • 2
    • 3
    Email author
  • Zhongning Lin
    • 1
    Email author
  • Chengyong He
    • 1
    Email author
  1. 1.State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Public HealthXiamen UniversityXiamenPeople’s Republic of China
  2. 2.Research Institute for Biomimetics and Soft MatterXiamen UniversityXiamenPeople’s Republic of China
  3. 3.Department of PhysicsNational University of SingaporeSingaporeSingapore

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