Klf4 , Klf2 , and Zfp148 activate autophagy‐related genes in smooth muscle cells during aortic aneurysm formation
Open Access
- 25 April 2019
- journal article
- research article
- Published by Wiley in Physiological Reports
- Vol. 7 (8), e14058
- https://doi.org/10.14814/phy2.14058
Abstract
Abdominal aortic aneurysms (AAAs) are a progressive dilation of the aorta that is characterized by an initial influx of inflammatory cells followed by a pro‐inflammatory, migratory, proliferative, and eventually apoptotic smooth muscle cell phenotype. In recent years, the mechanisms related to the initial influx of inflammatory cells have become well‐studied; the mechanisms related to chronic aneurysm formation, smooth muscle cell apoptosis and death are less well‐characterized. Autophagy is a generally believed to be a protective cellular mechanism that functions to recycle defective proteins and cellular organelles to maintain cellular homeostasis. Our goal with the present study was to investigate the role of autophagy in smooth muscle cells during AAA formation. Levels of the autophagy factors, Beclin, and LC3 were elevated in human and mouse AAA tissue via both qPCR and immunohistochemical analysis. Confocal staining in human and mouse AAA tissue demonstrated Beclin and LC3 were present in smooth muscle cells during AAA formation. Treatment of smooth muscle cells with porcine pancreatic elastase or interleukin (IL)‐1β activated autophagy‐related genes in vitro while treatment with a siRNA to Kruppel‐like transcription factor 4 (Klf4), Kruppel‐like transcription factor 2 (Klf2) or Zinc‐finger protein 148 (Zfp148) separately inhibited activation of autophagy genes. Chromatin immunoprecipitation assays demonstrated that Klf4, Klf2, and Zfp148 separately bind autophagy genes in smooth muscle cells following elastase treatment. These results demonstrate that autophagy is an important mechanism related to Klfs in smooth muscle cells during AAA formation.Keywords
Funding Information
- Thoracic Surgery Foundation for Research and Education
This publication has 52 references indexed in Scilit:
- Bone marrow–derived MCP1 required for experimental aortic aneurysm formation and smooth muscle phenotypic modulationThe Journal of Thoracic and Cardiovascular Surgery, 2011
- Overexpression of Transcription Factor Sp2 Inhibits Epidermal Differentiation and Increases Susceptibility to Wound- and Carcinogen-Induced TumorigenesisCancer Research, 2010
- KLF3 Regulates Muscle-Specific Gene Expression and Synergizes with Serum Response Factor on KLF Binding SitesMolecular and Cellular Biology, 2010
- Smooth muscle phenotypic modulation is an early event in aortic aneurysmsThe Journal of Thoracic and Cardiovascular Surgery, 2009
- Over-expression of the transcription factor, ZBP-89, leads to enhancement of the C2C12 myogenic programBiochimica et Biophysica Acta (BBA) - Molecular Cell Research, 2009
- The transcriptional repressor ZBP-89 and the lack of Sp1/Sp3, c-Jun and Stat3 are important for the down-regulation of the vimentin gene during C2C12 myogenesisDifferentiation, 2009
- Krüppel-like factor 4, Elk-1, and histone deacetylases cooperatively suppress smooth muscle cell differentiation markers in response to oxidized phospholipidsAmerican Journal of Physiology-Cell Physiology, 2008
- Hemizygous Deficiency of Krüppel-Like Factor 2 Augments Experimental AtherosclerosisCirculation Research, 2008
- Conditional Deletion of Krüppel-Like Factor 4 Delays Downregulation of Smooth Muscle Cell Differentiation Markers but Accelerates Neointimal Formation Following Vascular InjuryCirculation Research, 2008
- Kruppel-like factor 2 (KLF2) regulates proinflammatory activation of monocytesProceedings of the National Academy of Sciences of the United States of America, 2006