The Phosphatidylcholine Transfer Protein Stard7 is Required for Mitochondrial and Epithelial Cell Homeostasis

Mice fed a methionine- and choline-deficient (MCD) diet develop steatohepatitis that recapitulates key features of nonalcoholic steatohepatitis (NASH) in humans. Phosphatidylcholine is the most abundant phospholipid in the surfactant monolayer that coats and stabilizes lipid droplets within cells, and choline is required for its major biosynthetic pathway. Phosphatidylcholine-transfer protein (PC-TP), which exchanges phosphatidylcholines among membranes, is enriched in hepatocytes. PC-TP also regulates fatty acid metabolism through interactions with thioesterase superfamily member 2. We investigated the contribution of PC-TP to steatohepatitis induced by the MCD diet. Pctp−/− and wild-type control mice were fed the MCD diet for 5 wk and were then euthanized for histopathologic and biochemical analyses, as well as determinations of mRNA and protein expression. Whereas all mice developed steatohepatitis, plasma alanine aminotransferase and aspartate aminotransferase activities were only elevated in wild-type mice, indicating that Pctp−/− mice were protected from MCD diet-induced hepatocellular injury. Reduced hepatotoxicity due to the MCD diet in the absence of PC-TP expression was further evidenced by decreased activation of c-Jun and reduced plasma concentrations of fibroblast growth factor 21. Despite similar total hepatic concentrations of phosphatidylcholines and other lipids, the relative abundance of microvesicular lipid droplets within hepatocytes was reduced in Pctp−/− mice. Considering that the formation of larger lipid droplets may serve to protect against lipotoxicity in NASH, our findings suggest a pathogenic role for PC-TP that could be targeted in the management of this condition. NEW & NOTEWORTHY Phosphatidylcholine-transfer protein (PC-TP) is a highly specific phosphatidylcholine-binding protein that we previously showed to regulate hepatocellular nutrient metabolism through its interacting partner thioesterase superfamily member 2 (Them2). This study identifies a pathogenic role for PC-TP, independent of Them2, in the methionine- and choline-deficient diet model of experimental steatohepatitis. Our current observations suggest that PC-TP promotes liver injury by mediating the intermembrane transfer of phosphatidylcholines, thus stabilizing more pathogenic microvesicular lipid droplets.

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IL-17 in the lung: the good, the bad, and the ugly

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.00344.2017 ◽

2018 ◽

Vol 314 (1) ◽

pp. L6-L16 ◽

Cited By ~ 37

Author(s):

Stephen J. Gurczynski ◽

Bethany B. Moore

Keyword(s):

Epithelial Cell ◽

Pulmonary Fibrosis ◽

Mucosal Barrier ◽

Aberrant Expression ◽

Cell Homeostasis ◽

Cell Repair ◽

Beneficial Effects ◽

Bacteria And Fungi

The IL-17 family of cytokines has emerged over the last two decades as a pleiotropic group of molecules that function in a wide variety of both beneficial and detrimental (pathological) processes, mainly in mucosal barrier tissue. The beneficial effects of IL-17 expression are especially important in the lung, where exposure to foreign agents is abundant. IL-17A plays an important role in protection from both extracellular bacteria and fungi, as well as viruses that infect cells of the mucosal tracts. IL-17 coregulated cytokines, such as IL-22, are involved in maintaining epithelial cell homeostasis and participate in epithelial cell repair/regeneration following inflammatory insults. Thus, the IL-17/IL-22 axis is important in both responding to, and recovering from, pathogens. However, aberrant expression or overexpression of IL-17 cytokines contributes to a number of pathological outcomes, including asthma, pneumonitis, and generation or exacerbation of pulmonary fibrosis. This review covers the good, bad, and ugly aspects of IL-17 in the lung.

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In vitro Evidence that Phospholipid Secretion into Bile May Be Coordinated Intracellularly by the Combined Actions of Bile Salts and the Specific Phosphatidylcholine Transfer Protein of Liver

Biochemistry ◽

10.1021/bi00199a021 ◽

1994 ◽

Vol 33 (33) ◽

pp. 9975-9980 ◽

Cited By ~ 51

Author(s):

David E. Cohen ◽

Monika R. Leonard ◽

Martin C. Carey

Keyword(s):

Bile Salts ◽

Transfer Protein ◽

Combined Actions ◽

Phosphatidylcholine Transfer Protein

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