Endoplasmic reticulum stress contributes to ferritin molecules-mediated macrophage migration via P-selectin glycoprotein ligand-1

Chi Mei Wang, Yue-Hwa Chen, Yu Chieh Lee, Jung-Su Chang

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2 Citations (Scopus)

Abstract

Scope: Obesity is associated with elevated serum ferritin and increased macrophage activation and infiltration; however, the causal mechanisms underlying this relationship remain undefined. Methods and results: Serum ferritin and soluble P-selectin glycoprotein ligand (sPSGL)-1 level were higher in obese adolescents and patients with moderate nonalcoholic fatty liver disease (NAFLD) compared with controls (all p < 0.05). Multivariate linear regression revealed that serum ferritin was independently associated with sPSGL-1 (B = 0.249, 95% confidence interval: 0.011-0.487, p = 0.041) after adjustment for covariates. The messenger (m) RNA expression of GRP78/Bip, ferritin, and PSGL-1 in leukocytes was greater in patients with nonalcoholic fatty liver disease than in controls. An animal study showed that a tunicamycin injection (an endoplasmic reticulum stress inducer) triggered serum sPSGL-1 and ferritin elevation (all p < 0.01). An in vitro study revealed that serum ferritin and apoferritin induced tumor necrosis factor-α and sPSGL-1 secretion (all p < 0.01). A wound healing assay showed that PSGL-1 blocking inhibited apoferritin-mediated macrophage migration. GRP78/Bip knockdown by the endotoxin EGF-SubA completely inhibited apoferritin-mediated macrophage migration and PSGL-1 expression at the protein and mRNA levels (all p < 0.05). Conclusion: ER stress associated mechanisms are required for apoferritin-/ferritin-mediated macrophage migration via the PSGL-1-dependent pathway.

Original languageEnglish
JournalMolecular Nutrition and Food Research
DOIs
Publication statusPublished - 2017

Fingerprint

Endoplasmic Reticulum Stress
ferritin
Ferritins
endoplasmic reticulum
macrophages
Apoferritins
Macrophages
Serum
fatty liver
tunicamycin
macrophage activation
Tunicamycin
Messenger RNA
Macrophage Activation
tumor necrosis factors
endotoxins
P-selectin ligand protein
P-glycoproteins
ligands
tissue repair

Keywords

  • Apoferritin, Endoplasmic reticulum stress
  • Macrophage
  • Obesity
  • P-selectin glycoprotein-1
  • Serum ferritin

ASJC Scopus subject areas

  • Biotechnology
  • Food Science

Cite this

@article{6389d5ce27d843e7a5577a628a4c9961,
title = "Endoplasmic reticulum stress contributes to ferritin molecules-mediated macrophage migration via P-selectin glycoprotein ligand-1",
abstract = "Scope: Obesity is associated with elevated serum ferritin and increased macrophage activation and infiltration; however, the causal mechanisms underlying this relationship remain undefined. Methods and results: Serum ferritin and soluble P-selectin glycoprotein ligand (sPSGL)-1 level were higher in obese adolescents and patients with moderate nonalcoholic fatty liver disease (NAFLD) compared with controls (all p < 0.05). Multivariate linear regression revealed that serum ferritin was independently associated with sPSGL-1 (B = 0.249, 95{\%} confidence interval: 0.011-0.487, p = 0.041) after adjustment for covariates. The messenger (m) RNA expression of GRP78/Bip, ferritin, and PSGL-1 in leukocytes was greater in patients with nonalcoholic fatty liver disease than in controls. An animal study showed that a tunicamycin injection (an endoplasmic reticulum stress inducer) triggered serum sPSGL-1 and ferritin elevation (all p < 0.01). An in vitro study revealed that serum ferritin and apoferritin induced tumor necrosis factor-α and sPSGL-1 secretion (all p < 0.01). A wound healing assay showed that PSGL-1 blocking inhibited apoferritin-mediated macrophage migration. GRP78/Bip knockdown by the endotoxin EGF-SubA completely inhibited apoferritin-mediated macrophage migration and PSGL-1 expression at the protein and mRNA levels (all p < 0.05). Conclusion: ER stress associated mechanisms are required for apoferritin-/ferritin-mediated macrophage migration via the PSGL-1-dependent pathway.",
keywords = "Apoferritin, Endoplasmic reticulum stress, Macrophage, Obesity, P-selectin glycoprotein-1, Serum ferritin",
author = "Wang, {Chi Mei} and Yue-Hwa Chen and Lee, {Yu Chieh} and Jung-Su Chang",
year = "2017",
doi = "10.1002/mnfr.201600458",
language = "English",
journal = "Molecular Nutrition and Food Research",
issn = "1613-4125",
publisher = "Wiley-VCH Verlag",

}

TY - JOUR

T1 - Endoplasmic reticulum stress contributes to ferritin molecules-mediated macrophage migration via P-selectin glycoprotein ligand-1

AU - Wang, Chi Mei

AU - Chen, Yue-Hwa

AU - Lee, Yu Chieh

AU - Chang, Jung-Su

PY - 2017

Y1 - 2017

N2 - Scope: Obesity is associated with elevated serum ferritin and increased macrophage activation and infiltration; however, the causal mechanisms underlying this relationship remain undefined. Methods and results: Serum ferritin and soluble P-selectin glycoprotein ligand (sPSGL)-1 level were higher in obese adolescents and patients with moderate nonalcoholic fatty liver disease (NAFLD) compared with controls (all p < 0.05). Multivariate linear regression revealed that serum ferritin was independently associated with sPSGL-1 (B = 0.249, 95% confidence interval: 0.011-0.487, p = 0.041) after adjustment for covariates. The messenger (m) RNA expression of GRP78/Bip, ferritin, and PSGL-1 in leukocytes was greater in patients with nonalcoholic fatty liver disease than in controls. An animal study showed that a tunicamycin injection (an endoplasmic reticulum stress inducer) triggered serum sPSGL-1 and ferritin elevation (all p < 0.01). An in vitro study revealed that serum ferritin and apoferritin induced tumor necrosis factor-α and sPSGL-1 secretion (all p < 0.01). A wound healing assay showed that PSGL-1 blocking inhibited apoferritin-mediated macrophage migration. GRP78/Bip knockdown by the endotoxin EGF-SubA completely inhibited apoferritin-mediated macrophage migration and PSGL-1 expression at the protein and mRNA levels (all p < 0.05). Conclusion: ER stress associated mechanisms are required for apoferritin-/ferritin-mediated macrophage migration via the PSGL-1-dependent pathway.

AB - Scope: Obesity is associated with elevated serum ferritin and increased macrophage activation and infiltration; however, the causal mechanisms underlying this relationship remain undefined. Methods and results: Serum ferritin and soluble P-selectin glycoprotein ligand (sPSGL)-1 level were higher in obese adolescents and patients with moderate nonalcoholic fatty liver disease (NAFLD) compared with controls (all p < 0.05). Multivariate linear regression revealed that serum ferritin was independently associated with sPSGL-1 (B = 0.249, 95% confidence interval: 0.011-0.487, p = 0.041) after adjustment for covariates. The messenger (m) RNA expression of GRP78/Bip, ferritin, and PSGL-1 in leukocytes was greater in patients with nonalcoholic fatty liver disease than in controls. An animal study showed that a tunicamycin injection (an endoplasmic reticulum stress inducer) triggered serum sPSGL-1 and ferritin elevation (all p < 0.01). An in vitro study revealed that serum ferritin and apoferritin induced tumor necrosis factor-α and sPSGL-1 secretion (all p < 0.01). A wound healing assay showed that PSGL-1 blocking inhibited apoferritin-mediated macrophage migration. GRP78/Bip knockdown by the endotoxin EGF-SubA completely inhibited apoferritin-mediated macrophage migration and PSGL-1 expression at the protein and mRNA levels (all p < 0.05). Conclusion: ER stress associated mechanisms are required for apoferritin-/ferritin-mediated macrophage migration via the PSGL-1-dependent pathway.

KW - Apoferritin, Endoplasmic reticulum stress

KW - Macrophage

KW - Obesity

KW - P-selectin glycoprotein-1

KW - Serum ferritin

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DO - 10.1002/mnfr.201600458

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SN - 1613-4125

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