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Expression and Characterization of Transcription factor EB in Coronary Arterial Smooth Muscle Cells
Author(s) -
Bao Renyue,
Zuo Ping,
Li Xiang,
Li PinLan,
Zhang Yang
Publication year - 2017
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.31.1_supplement.826.4
Subject(s) - tfeb , autophagy , lysosome , microbiology and biotechnology , biology , transcription factor , biochemistry , gene , enzyme , apoptosis
Background We recently demonstrated that lysosome injury associated with abnormal sphingolipid metabolism causes impaired autophagic flux in coronary arterial smooth muscle cells (CASMCs). Under atherogenic stimulation, such impaired autophagic flux accelerates dedifferentiation of CASMCs to a synthetic phenotype. In the present study, we hypothesized that transcription factor EB (TFEB), a master regulator of lysosome biogenesis and autophagy signaling is involved in lysosome injury‐associated CASMC dedifferentiation. Methods CASMCs were primarily cultured from mouse coronary arterial arteries and used in this study. The mRNA and protein expression of TFEB in CASMCs were detected by real time quantitative PCR and Western blot, respectively. The activation of TFEB was determined by nuclear translocation of TFEB using immunofluorescence microscopy. Results and conclusion Lysosome functional inhibitors increased TFEB expression and activation in CASMCs, which was associated with up‐regulation of lysosome and autophagy markers. These results indicate that TFEB are expressed and functioning in CASMCs. Genetic deficiency of acid sphingomyelinase (ASM) results in enhanced cell proliferation and migration of CASMCs upon platelet‐derived growth factor (PDGF) stimulation. Such phenotypic changes in ASM‐deficient CAMSCs were associated with decreased nuclear translocation of TFEB compared to that in wild‐type cells. These results suggest that ASM/TFEB signaling axis is involved in the regulation of cell cycle in CASMCs implicating a novel role of TFEB in vascular smooth muscle plasticity. Support or Funding Information Supported by NIH grants HL057244, HL122769 and HL122937