Premium
Cytokine‐induced expression of the p75 neurotrophin receptor (p75) in vascular smooth muscle cells (p75)
Author(s) -
Kraemer Rosemary,
Novikov Nikolay,
Hempstead Barbara
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a68-c
Subject(s) - low affinity nerve growth factor receptor , cytokine , receptor , apoptosis , microbiology and biotechnology , tumor necrosis factor alpha , biology , in vivo , tunel assay , nerve growth factor , cancer research , immunology , biochemistry
SMC apoptosis regulates lesion development and plaque remodeling in atherogenesis. p75 is a regulator of SMC apoptosis in vivo. The expression of p75, and its ligands, the proneurotrophins, is up regulated in neointimal SMCs in regions of acute and chronic injury and there is decreased apoptosis and increased in lesion development in the ligated carotid artery of p75 −/− mice. The pro form of nerve growth factor (proNGF) induces apoptosis of transfected p75‐SMCs. The molecular mechanisms regulating p75 expression in SMCs is unknown. Here we identify factors that increase the expression of endogenous p75 in SMCs. Human aortic SMCs (HASMC) treated with both interferon γ and tumor necrosis factor α for 48 hours increases p75 protein expression and steady state mRNA levels by 2–5 fold, as assessed by Western blot analysis and real time PCR, respectively. HASMC express Sortilin, a binding partner for proNGF, and its expression is not changed by cytokine treatment. TUNEL analysis demonstrates that proNGF induces a 2‐fold increase in apoptosis of cytokine‐treated, but not control, HASMC and this response is blocked by the Sortilin ligand, neurotensin, confirming that the p75/Sortilin receptor complex mediates this response. These results are the first to demonstrate cytokine‐regulated expression of p75 in SMC. Thus, these cells represent neointimal SMCs in vivo and offer a primary SMC system to assess p75 activity in vitro. These studies were supported by NIH PO1 HL‐072942 and AHA GIA 0655783T .