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MANF protects human pancreatic beta cells against stress-induced cell death

Elina Hakonen1,2, Vikash Chandra3, Christopher L Fogarty4

  • 1Research Programs Unit, Molecular Neurology, Biomedicum Helsinki, University of Helsinki, PO Box 63, (Haartmaninkatu 8), 00014, Helsinki, Finland.

Diabetologia
|July 23, 2018
PubMed
Abstract

Insights

Mesencephalic astrocyte-derived neurotrophic factor (MANF) protects human beta cells from inflammatory stress and promotes proliferation. This suggests MANF is a potential therapeutic agent for diabetes by safeguarding pancreatic beta cells.

Area of Science:

  • Cell Biology
  • Endocrinology
  • Immunology

Background:

  • Pancreatic beta cell loss contributes to diabetes development.
  • Endoplasmic reticulum (ER) stress is implicated in beta cell apoptosis.
  • Mesencephalic astrocyte-derived neurotrophic factor (MANF) is an ER stress-inducible protein with potential roles in cell survival.

Purpose of the Study:

  • To investigate the protective potential of MANF against ER stress-induced apoptosis in human beta cells.
  • To explore MANF's effects on beta cell proliferation and underlying mechanisms.

Main Methods:

  • Human islets and EndoC-βH1 cells were challenged with proinflammatory cytokines, with or without recombinant human MANF.
  • Cell viability, ER stress markers, and proliferation were assessed.
  • Global transcriptomic analysis and pathway analysis were performed.

Main Results:

  • MANF significantly reduced cytokine-induced beta cell death by 38%.
  • MANF inhibited ER stress and NF-κB signaling pathway activation.
  • MANF treatment doubled primary human beta cell proliferation when TGF-β signaling was inhibited.

Conclusions:

  • Exogenous MANF protein protects human beta cells from inflammatory stress-induced apoptosis.
  • MANF exhibits antiapoptotic and mitogenic properties, positioning it as a potential therapeutic agent for beta cell protection in diabetes.
Keywords:
Beta cell proliferationBeta cell protectionEndoplasmic reticulum stressMesencephalic astrocyte-derived neurotrophic factor (MANF)NF-κB

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