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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
Author(s) -
Jia Guanghong,
Cheng Gang,
Gangahar Deepak M,
Agrawal Devendra K
Publication year - 2006
Publication title -
immunology and cell biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.999
H-Index - 104
eISSN - 1440-1711
pISSN - 0818-9641
DOI - 10.1111/j.1440-1711.2006.01454.x
Subject(s) - autophagy , protein kinase b , vascular smooth muscle , microbiology and biotechnology , c jun , biology , signal transduction , programmed cell death , growth factor , kinase , pi3k/akt/mtor pathway , apoptosis , chemistry , endocrinology , transcription factor , biochemistry , gene , receptor , smooth muscle
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.