@article{a6c561a4ece94ae8b966ac7bbe6896df,
title = "Lysophosphatidic acid stimulates pericyte migration via LPA receptor 1",
abstract = "Lysophosphatidic acid (LPA) is a bioactive compound known to regulate various vascular functions. However, despite the fact that many vascular functions are regulated by peri-vascular cells such as pericytes, the effect of LPA on brain pericytes has not been fully evaluated. Thus, we designed this study to evaluate the effects of LPA on brain pericytes. These experiments revealed that while LPA receptors (LPARs) are expressed in cultured pericytes from mouse brains, LPA treatment does not influence the proliferation of these cells but does have a profound impact on their migration, which is regulated via the expression of LPAR1. LPAR1 expression was also detected in human pericyte culture and LPA treatment of these cells also induced migration. Taken together these findings imply that LPA-LPAR1 signaling is one of the key mechanisms modulating pericyte migration, which may help to control vascular function during development and repair processes.",
keywords = "AM095, Autotaxin, Brain, Human, Mouse, Repair",
author = "Yoshino Yonezu and Shogo Tanabe and Hidemi Misawa and Rieko Muramatsu",
note = "Funding Information: CNS pericytes line various endothelial tubes, including pre-capillary arterioles, capillaries, and post-capillary venules. During development and angiogenesis, pericytes can migrate away from the capillary surface and facilitate endothelial cell sprouting creating novel vascular structures that are then wrapped in pericytes which stabilize these nascent structures allowing them to mature [19]. This suggests that pericyte migration is a crucial process in vascular response making it critical to homeostasis and tissue health. This migration is known to be regulated by several factors derived from both endothelial cells and the extracellular matrix, such as heparin-binding epidermal growth factor [20] and fibronectin [21]. In contrast, LPA, a newly described signaling factor, regulates pericyte migration and is known to be highly presented in the plasma, especially when compared to the CNS [8]. LPC, as the LPA precursor, is primarily produced in the liver of normal adult humans [22], demonstrating that pericyte functions within the CNS are affected by the systemic environment; this is in agreement with another study that indicated that CNS angiogenesis in aged mice can be induced by the upregulation of systemic growth differentiation factor 11 from young mice [23]. In addition, another study linked remyelination failures in aging populations to a decline in the concentrations of circulating apelin [24], supporting the hypothesis that various CNS functions may be regulated in a systemic manner.In summary, our data shows that LPA-LPAR1 promotes pericyte migration, which is crucial for not only vascular development/maintenance, but also for neuronal regeneration after injury. CNS injury leads to severe neurological deficits in motor, sensory, and other functions, and mechanical damage to the neuronal network is characterized by limited regeneration, with these lesions often being sealed with scar tissue produced from a specific type of pericyte (Type A) [34,35]. Thus, we suggest that LPA-LPAR interactions may control secondary neuronal regeneration and the creation of specific scar tissues. This is supported by the fact that aberrant LPA levels have been reported in several neurological disorders, including multiple sclerosis [36], amyotrophic lateral sclerosis [37], Alzheimer's disease [38], and Parkinson's disease [39], leading us to speculate that LPA may be a novel therapeutic target for treating CNS diseases.This work was supported by Grants-in-Aid for Scientific Research from the Japanese Society for the Promotion of Science (grant no. 19H03554 to R.M.) and AMED (grant no. JP22gm6210020 to R.M.). Publisher Copyright: {\textcopyright} 2022 Elsevier Inc.",
year = "2022",
month = aug,
day = "27",
doi = "10.1016/j.bbrc.2022.06.016",
language = "English",
volume = "618",
pages = "61--66",
journal = "Biochemical and Biophysical Research Communications",
issn = "0006-291X",
publisher = "Academic Press Inc.",
}