title: Role of LPA and the Hippo pathway on apoptosis in salivary gland epithelial cells.
abstract: Lysophosphatidic acid (LPA) is a bioactive lysophospholipid involved in numerous physiological responses. However, the expression of LPA receptors and the role of the Hippo signaling pathway in epithelial cells have remained elusive. In this experiment, we studied the functional expression of LPA receptors and the associated signaling pathway using reverse transcriptase-PCR, microspectrofluorimetry, western blotting and immunocytochemistry in salivary gland epithelial cells. We found that LPA receptors are functionally expressed and involved in activating the Hippo pathway mediated by YAP/TAZ through Lats/Mob1 and RhoA/ROCK. Upregulation of YAP/TAZ-dependent target genes, including CTGF, ANKRD1 and CYR61, has also been observed in LPA-treated cells. In addition, based on data suggesting that tumor necrosis factor (TNF)-α induces cell apoptosis, LPA upregulates TNF-induced caspase-3 and cleaved Poly(ADP-ribose)polymerase (PARP). However, small interfering RNA treatment to Yes-associated protein (YAP) or transcriptional co-activator with a PDZ-binding motif (TAZ) significantly decreased TNF-α- and LPA-induced apoptosis, suggesting that YAP and TAZ modulate the apoptotic pathway in salivary epithelial cells.
authors.affiliation: Department of Physiology, School of Dentistry, Seoul National University and Dental Research Institute, ChongnoKu, Seoul, Korea.
authors.forename: Sung-Min
authors.initials: SM
authors.lastname: Hwang
authors.affiliation: Department of Physiology, School of Dentistry, Seoul National University and Dental Research Institute, ChongnoKu, Seoul, Korea.
authors.forename: MeiHong
authors.initials: M
authors.lastname: Jin
authors.affiliation: Department of Physiology, School of Dentistry, Seoul National University and Dental Research Institute, ChongnoKu, Seoul, Korea.
authors.forename: Yong Hwan
authors.initials: YH
authors.lastname: Shin
authors.affiliation: Department of Physiology, School of Dentistry, Seoul National University and Dental Research Institute, ChongnoKu, Seoul, Korea.
authors.forename: Seul
authors.initials: S
authors.lastname: Ki Choi
authors.affiliation: Department of Physiology, School of Dentistry, Seoul National University and Dental Research Institute, ChongnoKu, Seoul, Korea.
authors.forename: Eun
authors.initials: E
authors.lastname: Namkoong
authors.affiliation: Department of Physiology, School of Dentistry, Seoul National University and Dental Research Institute, ChongnoKu, Seoul, Korea.
authors.forename: MinKyoung
authors.initials: M
authors.lastname: Kim
authors.affiliation: Department of Physiology, School of Dentistry, Seoul National University and Dental Research Institute, ChongnoKu, Seoul, Korea.
authors.forename: Moon-Yong
authors.initials: MY
authors.lastname: Park
authors.affiliation: Department of Physiology, School of Dentistry, Seoul National University and Dental Research Institute, ChongnoKu, Seoul, Korea.
authors.forename: Kyungpyo
authors.initials: K
authors.lastname: Park
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism; D017209:Apoptosis; D002460:Cell Line; D004847:Epithelial Cells / Q000166:cytology* / Q000378:metabolism; D005786:Gene Expression Regulation; D000090683:Hippo Signaling Pathway; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D008246:Lysophospholipids / Q000378:metabolism*; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D049368:Receptors, Lysophosphatidic Acid / Q000235:genetics / Q000378:metabolism*; D012469:Salivary Glands / Q000166:cytology* / Q000378:metabolism; D015398:Signal Transduction; D015534:Trans-Activators; D014157:Transcription Factors; D000091364:Transcriptional Coactivator with PDZ-Binding Motif Proteins; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D000091102:YAP-Signaling Proteins; D054460:rho-Associated Kinases / Q000378:metabolism; D020742:rhoA GTP-Binding Protein / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D047908:Intracellular Signaling Peptides and Proteins; D008246:Lysophospholipids; D010750:Phosphoproteins; D034741:RNA, Small Interfering; D049368:Receptors, Lysophosphatidic Acid; D015534:Trans-Activators; D014157:Transcription Factors; D000091364:Transcriptional Coactivator with PDZ-Binding Motif Proteins; D014409:Tumor Necrosis Factor-alpha; C551991:WWTR1 protein, human; D000091102:YAP-Signaling Proteins; C088374:YAP1 protein, human; C066737:RHOA protein, human; D017346:Protein Serine-Threonine Kinases; D054460:rho-Associated Kinases; D020742:rhoA GTP-Binding Protein; C032881:lysophosphatidic acid