title: Phospholipase D1 decreases type I collagen levels in hepatic stellate cells via induction of autophagy.
abstract: Hepatic stellate cells (HSCs) are major players in liver fibrogenesis. Accumulating evidence shows that suppression of autophagy plays an important role in the development and progression of liver disease. Phospholipase D1 (PLD1), which catalyzes the hydrolysis of phosphatidylcholine to yield phosphatidic acid (PA) and choline, was recently shown to modulate autophagy. However, little is known about the effects of PLD1 on the production of type I collagen that characterizes liver fibrosis. Here, we examined whether PLD1 regulates type I collagen levels in HSCs through induction of autophagy. Adenovirus-mediated overexpression of PLD-1 (Ad-PLD1) reduced type I collagen levels in the activated human HSC lines, hTERT and LX2. Overexpression of PLD1 in HSCs led to induction of autophagy as demonstrated by increased LC3-II conversion and formation of LC3 puncta, and decreased p62 abundance. Moreover, inhibiting the induction of autophagy by treating cells with bafilomycin or a small interfering (si)RNA for ATG7 rescued Ad-PLD1-induced suppression of type I collagen accumulation in HSCs. The effects of PLD on type I collagen levels were not related to TGF-β/Smad signaling. Furthermore, treatment of cells with PA induced autophagy and inhibited type I collagen accumulation. The present study indicates that PLD1 plays a role in regulating type I collagen accumulation through induction of autophagy.
authors.affiliation: Division of Endocrinology and Metabolism, Department of Internal Medicine, Keimyung University School of Medicine, Daegu, South Korea.
authors.forename: H-Y
authors.initials: HY
authors.lastname: Seo
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, Keimyung University School of Medicine, Daegu, South Korea.
authors.forename: B-K
authors.initials: BK
authors.lastname: Jang
authors.affiliation: Division of Endocrinology and Metabolism, Department of Internal Medicine, Keimyung University School of Medicine, Daegu, South Korea.
authors.forename: Y-A
authors.initials: YA
authors.lastname: Jung
authors.affiliation: Division of Endocrinology and Metabolism, Department of Internal Medicine, Keimyung University School of Medicine, Daegu, South Korea.
authors.forename: E-J
authors.initials: EJ
authors.lastname: Lee
authors.affiliation: Division of Endocrinology and Metabolism, Department of Internal Medicine, Keimyung University School of Medicine, Daegu, South Korea.
authors.forename: H-S
authors.initials: HS
authors.lastname: Kim
authors.affiliation: Division of Endocrinology and Metabolism, Department of Internal Medicine, Kyungpook National University School of Medicine, Daegu, South Korea.
authors.forename: J-H
authors.initials: JH
authors.lastname: Jeon
authors.affiliation: Division of Endocrinology and Metabolism, Department of Internal Medicine, Kyungpook National University School of Medicine, Daegu, South Korea.
authors.forename: J-G
authors.initials: JG
authors.lastname: Kim
authors.affiliation: Division of Endocrinology and Metabolism, Department of Internal Medicine, Kyungpook National University School of Medicine, Daegu, South Korea.
authors.forename: I-K
authors.initials: IK
authors.lastname: Lee
authors.affiliation: Division of Endocrinology and Metabolism, Department of Internal Medicine, Keimyung University School of Medicine, Daegu, South Korea. Electronic address: mdkmk@dsmc.or.kr.
authors.forename: M-K
authors.initials: MK
authors.lastname: Kim
authors.affiliation: Division of Endocrinology and Metabolism, Department of Internal Medicine, Kyungpook National University School of Medicine, Daegu, South Korea. Electronic address: kpark@knu.ac.kr.
authors.forename: K-G
authors.initials: KG
authors.lastname: Park
mesh_terms: D001343:Autophagy / Q000502:physiology*; D002460:Cell Line; D024042:Collagen Type I / Q000378:metabolism*; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology; D055166:Hepatic Stellate Cells / Q000166:cytology* / Q000378:metabolism*; D006801:Humans; D010739:Phospholipase D / Q000378:metabolism*
chemical_list: D024042:Collagen Type I; D010739:Phospholipase D; C106801:phospholipase D1
keywords: Autophagy; Hepatic stellate cells; Phospholipase D1