Klf4, Klf2, and Zfp148 activate autophagy-related genes in smooth muscle cells during aortic aneurysm formation.

Morgan Salmon, Michael Spinosa, Zendra E Zehner, Gilbert R Upchurch, Gorav Ailawadi

Physiological reports 2019 Apr

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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. © 2019 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

Citation

Morgan Salmon, Michael Spinosa, Zendra E Zehner, Gilbert R Upchurch, Gorav Ailawadi. Klf4, Klf2, and Zfp148 activate autophagy-related genes in smooth muscle cells during aortic aneurysm formation. Physiological reports. 2019 Apr;7(8):e14058