4.7 Review

Lysophospholipids and their producing enzymes: Their pathological roles and potential as pathological biomarkers

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Lysophospholipid Mediators in Health and Disease

Kuniyuki Kano et al.

Summary: Lysophospholipids, such as lysophosphatidic acid (LPA) and sphingosine 1-phosphate (S1P), are important extracellular lipid mediators that signal through specific G protein-coupled receptors. They play crucial roles in various biological processes and diseases, including cellular stress signaling, inflammation, and host defense responses. LPA is involved in regulating fibrosis, neuropathic pain, abnormal angiogenesis, endometriosis, and neuroectodermal developmental disorders, while S1P controls collective behavior, apoptotic cell clearance, and immunesurveillance of cancers. The study of lysophospholipids has led to the development of new therapeutics for autoimmune diseases and holds promise for future treatments of fibrotic disorders, vascular diseases, and cancer.

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Lysophosphatidylcholine mediates fast decline in kidney function in diabetic kidney disease commentary

Kentaro Yoshioka et al.

Summary: In this study, a comprehensive metabolomic analysis was performed on patients with G3 stage DKD, and increased urinary LPC levels were identified in fast decliners. The increase in urinary LPC levels was associated with a decline in estimated glomerular filtration rate. A rat model of DKD also showed increased levels of LPC in urine and kidney tubulointerstitium as the disease progressed. In vitro studies confirmed that LPC induced lipotoxicity in proximal tubular cells. Therefore, LPC (16:0) and (18:0) may play a role in the fast progression of DKD and could be a target for novel therapeutic approaches.

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Urine autotaxin levels reflect the disease activity of sarcoidosis

Koji Murakami et al.

Summary: This study found that urine ATX levels may be a novel and useful indicator for assessing disease activity in sarcoidosis.

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The Many Roles of Lysophospholipid Mediators and Japanese Contributions to This Field

Yugo Takagi et al.

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Decrease in serum levels of autotaxin in COVID-19 patients

Takuya Shimura et al.

Summary: This study found that the serum levels of ATX were decreased in COVID-19 patients, irrespective of disease severity, and were negatively associated with serum markers of inflammation, blood coagulation, and antibodies. These findings suggest that the modulation of ATX may serve as a compensatory biological response to suppress immunological overreaction.

ANNALS OF MEDICINE (2022)

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Higher serum levels of autotaxin and phosphatidylserine-specific phospholipase A1 in patients with lupus nephritis

Yasunori Iwata et al.

Summary: In patients with lupus nephritis, serum levels of ATX and PS-PLA(1) were significantly higher, with lower levels of ATX associated with higher activity and chronicity scores. These results could be influenced by treatment, and further research is needed to clarify the clinical utility of these biomarkers in lupus nephritis.

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Ddhd1 knockout mouse as a model of locomotive and physiological abnormality in familial spastic paraplegia

Takuya Morikawa et al.

Summary: The novel homozygous 4-bp deletion in DDHD1 was identified as responsible for spastic paraplegia type 28 (SPG28). Knockout mice with a premature stop codon similar to the patient showed decreased foot-base angle and reduced LPI 20:4 (sn-2) levels in the cerebra. Changes in gene expression related to nervous system and cell-cell communication were also observed, suggesting a potential role of reduced downstream signaling in the pathogenesis of SPG28.

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Inhibition of autotaxin activity ameliorates neuropathic pain derived from lumbar spinal canal stenosis

Baasanjav Uranbileg et al.

Summary: The study indicated a potential link between elevated levels of LPC and LPA in cerebrospinal fluid and lumbar spinal canal stenosis. The use of an ATX inhibitor in a compression of DRG model showed promising results in alleviating pain symptoms and reducing populations of microglia and astrocytes in the spinal dorsal horn.

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Article Multidisciplinary Sciences

An ATX-LPA6-Gα13-ROCK axis shapes and maintains caudal vein plexus in zebrafish

Ryohei Okasato et al.

Summary: The study found that the ATX-LPA(6) axis cooperates with blood flow to generate contractile force in endothelial cells, contributing to the formation and maintenance of the CVP.

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Current Knowledge on the Biology of Lysophosphatidylserine as an Emerging Bioactive Lipid

Jumpei Omi et al.

Summary: LysoPS is an emerging lysophospholipid mediator that acts through G protein-coupled receptors and is mainly produced by the deacylation of phosphatidylserine. It stimulates degranulation of mast cells and has immune-modulatory functions through its specific GPCRs expressed in immune cells. Modulation of LysoPS signaling shows promise for therapies targeting immune diseases.

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Increase in serum levels of phosphatidylserine-specific phospholipase A1 in COVID-19 patients

Takuya Shimura et al.

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Phosphatidylserine-specific phospholipase A1: A friend or the devil in disguise

Yang Zhao et al.

Summary: PLA1A is an enzyme expressed in various human tissues and cells, involved in regulating immune cell maturation and function through hydrolyzing PS or 1-acyl-lysoPS. High levels of PLA1A expression are associated with autoimmune disorders, cancers, and cardiometabolic disorders. Additionally, PLA1A plays a role in hepatitis C virus assembly and antivirus innate immune response.

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Suppressing postcollection lysophosphatidic acid metabolism improves the precision of plasma LPA quantification

Kuniyuki Kano et al.

Summary: The study developed an optimized plasma preparation method to accurately measure LPA concentrations, revealing lower levels of LPA in humans and mice than previously reported. The increased accuracy also allowed for the detection of circadian rhythms in certain LPA species in mouse plasma.

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Elevated phosphatidylserine-specific phospholipase A1 level in hyperthyroidism

Kazuki Nakawatari et al.

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Identification and biochemical characterization of a second zebrafish autotaxin gene

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Serum autotaxin levels are associated with Graves' disease

Takahiro Nojiri et al.

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Performance of autotaxin as a serum marker for liver fibrosis

Hitoshi Ikeda et al.

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Lysophospholipids in laboratory medicine

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Autotaxin is Related to Metabolic Dysfunction and Predicts Alzheimer's Disease Outcomes

Kelsey E. McLimans et al.

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Autotaxin activity has a high accuracy to diagnose intrahepatic cholestasis of pregnancy

Andreas E. Kremer et al.

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Lipid phosphate phosphatases and their roles in mammalian physiology and pathology

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Separation and quantification of 2-acyl-1-lysophospholipids and 1-acyl-2-lysophospholipids in biological samples by LC-MS/MS

Michiyo Okudaira et al.

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Novel lysophosphoplipid receptors: their structure and function

Kumiko Makide et al.

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Increased autotaxin activity in multiple sclerosis

Hamid Zahednasab et al.

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Autotaxin in liver fibrosis

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Increased circulating plasma lysophosphatidic acid in patients with acute coronary syndrome

Tomotaka Dohi et al.

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Autotaxin as a novel serum marker of liver fibrosis

Hayato Nakagawa et al.

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Specific increase in serum autotaxin activity in patients with pancreatic cancer

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Generation of lysophosphatidylinositol by DDHD domain containing 1 (DDHD1): Possible involvement of phospholipase D/phosphatidic acid in the activation of DDHD1

Atsushi Yamashita et al.

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Serum lysophospholipase D/autotaxin may be a new nutritional assessment marker: study on prostate cancer patients

Kazuhiro Nakamura et al.

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Plasma lysophosphatidylcholine levels: Potential biomarkers for colorectal cancer

Zhenwen Zhao et al.

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Both plasma lysophosphatidic acid and serum autotaxin levels are increased in chronic hepatitis C

Naoko Watanabe et al.

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Human hair growth deficiency is linked to a genetic defect in the phospholipase gene LIPH

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Lysophosphatidic acid and autotaxin stimulate cell motility of neoplastic and non-neoplastic cells through LPA1

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