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Induction and Analysis of Epithelial to Mesenchymal Transition
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Induction and Analysis of Epithelial to Mesenchymal Transition

Published on: August 27, 2013

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Aβ inhibits mesenchymal stem cell-pericyte transition through MAPK pathway

Lixia Xu1, Jialin Li2, Zhongqiu Luo2

  • 1Tianjin Key Laboratory of Cerebral Vascular and Neurodegenerative Diseases, Tianjin Neurosurgical Institute, Tianjin, China.

Acta Biochimica Et Biophysica Sinica
|June 26, 2018
PubMed

Insights

Amyloid beta (Aβ) impairs pericyte differentiation, a crucial step in blood vessel formation, potentially contributing to Alzheimer's disease (AD) pathology. This study reveals Aβ inhibits pericyte marker expression via the ERK1/2 MAPK pathway.

Area of Science:

  • Neuroscience
  • Cell Biology
  • Vascular Biology

Background:

  • Pericyte loss is a hallmark of human Alzheimer's disease (AD) in the brain's hippocampus and cortex.
  • Pericyte differentiation and recruitment are vital for blood vessel development.
  • The specific impact of amyloid beta (Aβ) on pericyte differentiation remains unclear.

Purpose of the Study:

  • To investigate the interaction between Aβ and the differentiation of mesenchymal stem cells (MSCs) into pericytes.
  • To elucidate the mechanisms by which Aβ affects pericyte differentiation.

Main Methods:

  • Examined pericyte markers (desmin) in the cortex of APP/PS1 mice overexpressing Aβ.
  • Assessed the effect of Aβ40 and Aβ42 on pericyte marker expression (α-SMA, desmin, PDGFRβ) in cultured MSCs.
  • Investigated the role of the ERK1/2 MAPK signaling pathway in mediating Aβ's effects.

Main Results:

  • APP/PS1 mice showed significant pericyte loss compared to controls, indicated by reduced desmin expression.
  • Both Aβ40 and Aβ42 inhibited the expression of key pericyte markers in differentiating MSCs.
  • Aβ-induced inhibition of MSC-to-pericyte transition was mediated by the activation of the ERK1/2 MAPK pathway.

Conclusions:

  • Amyloid beta directly inhibits the differentiation of mesenchymal stem cells into pericytes.
  • The ERK1/2 MAPK pathway is a key mediator of Aβ's detrimental effects on pericyte differentiation.
  • Understanding Aβ's role in pericyte differentiation may offer new therapeutic targets for Alzheimer's disease.

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