mProX™ Human LPAR4 Stable Cell Line

Takai M, et al. "Induction of lysophosphatidic acid (LPA) receptor-mediated signaling regulates ." Advances in biological regulation, 2023.
Hydrogen peroxide (H(2)O(2)) is known to contribute to the development of cancer cells through reactive oxygen species (ROS). The effects of lysophosphatidic acid (LPA) signaling through LPA receptors (LPA(1) to LPA(6)) on cellular functions, such as growth, migration, and differentiation, have been widely observed. To investigate the relationship between LPA receptors and cell motility and survival in colon cancer cells, a study was conducted using colon cancer DLD-1 cells treated with H(2)O(2). Through two months of exposure to 60 muM H(2)O(2), the DLD-1 cells became DLD-H(2)O(2) cells with significantly elevated expression of LPAR2 and LPAR4 genes. These cells had decreased motility and heightened survival to anticancer drugs, including fluorouracil (5-FU), irinotecan (CPT-11), and oxaliplatin (L-OHP). Knockdown of LPA(2) in DLD-H(2)O(2) cells was found to decrease their sensitivity to 5-FU, while knockdown of LPA(4) had the opposite effect. Under hypoxic conditions, DLD-H(2)O(2) cells cultured at 1% O(2) exhibited enhanced survival to 5-FU compared to DLD-1 cells, with a correlation to LPAR2 gene expression. These findings indicate that LPA receptor-mediated signaling plays a crucial role in regulating cellular functions in H(2)O(2)-treated DLD-1 cells.
Pubmed: 37603941   DOI: 10.1016/j.jbior.2023.100978

Lee JW, et al. "SOX17-mediated LPAR4 expression plays a pivotal role in cardiac development and ." Experimental & molecular medicine, 2023.
Lysophosphatidic acid receptor 4 (LPAR4) is a protein that is briefly expressed during the cardiac progenitor stage of pluripotent stem cell (PSC)-derived cardiac differentiation. A team of researchers used RNA sequencing, promoter analyses, and loss-of-function studies in human PSCs to identify the essential role of SRY-box transcription factor 17 (SOX17) in regulating LPAR4 expression during cardiac differentiation. Subsequent mouse embryo analyses confirmed the sequential expression of SOX17 and LPAR4 during in vivo cardiac development. In a transplantation model using LPAR4 promoter-driven GFP cells, the team observed two types of LPAR4(+) cells in the heart following myocardial infarction (MI). These cells exhibited cardiac differentiation potential, with heart-resident LPAR4(+) cells being SOX17(+) while bone marrow-derived infiltrated LPAR4(+) cells did not demonstrate this ability. The researchers also explored various approaches to enhance cardiac repair by manipulating downstream signaling pathways of LPAR4. In the early stages of MI, inhibition of LPAR4 signaling using a p38 mitogen-activated protein kinase (p38 MAPK) blocker resulted in improved cardiac function and reduced fibrotic scarring compared to stimulation of LPAR4. These findings contribute to our understanding of heart development and suggest potential therapeutic strategies for enhancing repair and regeneration after injury by modulating LPAR4 signaling.
Pubmed: 37394586   DOI: 10.1038/s12276-023-01025-w