Insulin-like growth factor-1 and TNF-α regulate autophagy through c-jun N-terminal kinase and Akt pathways in human atherosclerotic vascular smooth cells

Guanghong Jia, Ganga Cheng, Deepak M. Gangahar, Devendra K. Agrawal

Research output: Contribution to journalArticle

214 Citations (Scopus)

Abstract

A balance between programmed cell death and survival of vascular smooth muscle cells (VSMC) in the fibrous cap, which is primarily composed of VSMC and extracellular matrix, appears to best correlate with plaque instability or stability and is controlled by growth factors and cytokines. Autophagy is also involved in programmed cell death. We assessed the effect of TNF-α and insulin-like growth factor-1 (IGF-1) on the expression of autophagic genes, microtubule-associated protein 1 light chain 3 (MAPLC-3) and Beclin-1 in VSMC isolated from atherosclerotic plaques. Transmission electron microscopy showed a significantly higher number of vacuolated cells in the TNF-α-treated VSMC and a markedly lower number in the IGF-1-treated VSMC when compared with the untreated control group. TNF-α-induced MAPLC-3 mRNA expression through c-jun N-terminal kinase and protein kinase B pathways and induced Beclin-1 protein expression through the c-jun N-terminal kinase pathway. Expression of MAPLC-3 and Beclin-1 correlated with autophagic cell death of plaque VSMC. IGF-1 inhibited MAPLC-3 mRNA transcripts through the Akt pathway. These findings suggest that the expression of autophagy genes can be influenced by IGF-1 and TNF-α through c-jun N-terminal kinase or Akt pathways and autophagy might be involved in the regulation of plaque stability.

Original languageEnglish
Pages (from-to)448-454
Number of pages7
JournalImmunology and Cell Biology
Volume84
Issue number5
DOIs
StatePublished - Oct 2006

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JNK Mitogen-Activated Protein Kinases
Autophagy
Somatomedins
Vascular Smooth Muscle
Smooth Muscle Myocytes
Blood Vessels
Muscle
Microtubule-Associated Proteins
Cell death
Light
Cells
Cell Death
Genes
Gene Expression
Proto-Oncogene Proteins c-akt
Messenger RNA
Atherosclerotic Plaques
Transmission Electron Microscopy
Extracellular Matrix
Cell Survival

All Science Journal Classification (ASJC) codes

  • Immunology
  • Clinical Biochemistry
  • Cell Biology

Cite this

Insulin-like growth factor-1 and TNF-α regulate autophagy through c-jun N-terminal kinase and Akt pathways in human atherosclerotic vascular smooth cells. / Jia, Guanghong; Cheng, Ganga; Gangahar, Deepak M.; Agrawal, Devendra K.

In: Immunology and Cell Biology, Vol. 84, No. 5, 10.2006, p. 448-454.

Research output: Contribution to journalArticle

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