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.

Hepatocyte TAZ/WWTR1 Promotes Inflammation and Fibrosis in Nonalcoholic Steatohepatitis

“…Little is known about the pro-inflammatory roles of TAZ, and, in general, YAP and TAZ inhibit rather than promote apoptosis during development and in cancer (Yu et al, 2015). However, there is one report showing that siTaz decreased TNFα-induced apoptosis in salivary gland epithelial cells (Hwang et al, 2014). RIP3-mediated necroptosis may also be important in hepatocyte death in NASH (Gautheron et al, 2014), and therefore it is possible that TAZ promotes this pathway.…”

Myocardin-Related Transcription Factor A and Yes-Associated Protein Exert Dual Control in G Protein-Coupled Receptor- and RhoA-Mediated Transcriptional Regulation and Cell Proliferation

“…At the same time, we examined three other genes, encoding alpha-smooth muscle actin (ACTA2), connective tissue growth factor (CTGF), and ankyrin repeat domain-containing protein 1 (ANKRD1), all of which are established MRTF-A-and YAP-regulated genes (7,31,(36)(37)(38)(39)(40). Knockdown of either YAP or MRTF-A fully abolished S1P-induced mRNA increases for all four of the genes (Fig.…”

Sphingosylphosphorylcholine regulates the Hippo signaling pathway in a dual manner

“…The original studies identifying S1P and LPA as YAP activators and studies expanding on LPAinduced Hippo regulation [20,21,48,49] implicated Rho or the Rho-ROCK pathway in mediating YAP activation. In contrast, in our experiments Rho-ROCK did not mediate the SPC-induced effects on either Lats2 or YAP, even though S1P 2 often couples to G 12/13 -Rho-ROCK [9].…”