Exp Mol Med.  2014 Dec;46(12):e125. 10.1038/emm.2014.77.

Role of LPA and the Hippo pathway on apoptosis in salivary gland epithelial cells

• Hwang SM
• Jin M
• Shin YH
• Ki Choi S
• Namkoong E
• Kim M
• Park MY
• Park K

• KMID: 2155390
• DOI: http://doi.org/10.1038/emm.2014.77

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)-alpha 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-alpha- and LPA-induced apoptosis, suggesting that YAP and TAZ modulate the apoptotic pathway in salivary epithelial cells.

MeSH Terms

Adaptor Proteins, Signal Transducing/genetics/metabolism
*Apoptosis
Cell Line
Epithelial Cells/*cytology/metabolism
Gene Expression Regulation
Humans
Intracellular Signaling Peptides and Proteins/genetics/metabolism
Lysophospholipids/*metabolism
Phosphoproteins/genetics/metabolism
Protein-Serine-Threonine Kinases/*metabolism
RNA Interference
RNA, Small Interfering/genetics
Receptors, Lysophosphatidic Acid/genetics/*metabolism
Salivary Glands/*cytology/metabolism
*Signal Transduction
Tumor Necrosis Factor-alpha/metabolism
rho-Associated Kinases/metabolism
rhoA GTP-Binding Protein/metabolism
Adaptor Proteins, Signal Transducing
Intracellular Signaling Peptides and Proteins
Lysophospholipids
Phosphoproteins
RNA, Small Interfering
Receptors, Lysophosphatidic Acid
Tumor Necrosis Factor-alpha
Protein-Serine-Threonine Kinases
rho-Associated Kinases
rhoA GTP-Binding Protein