Increased Levels of Renal Lysophosphatidic Acid in Rodent Models with Renal Disease
| Autor: | Richard J. Roman, Noriyuki Miyata, Stanley V. Smith, Takashi Hirata, Teisuke Takahashi |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Male medicine.medical_specialty Hypertension Renal medicine.drug_class Renal cortex urologic and male genital diseases Kidney Diabetic nephropathy Rats Sprague-Dawley 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Internal medicine Diabetes mellitus Lysophosphatidic acid Renal fibrosis Medicine Animals Diabetic Nephropathies Pharmacology Rats Inbred Dahl business.industry Isoxazoles Receptor antagonist medicine.disease Fibrosis Rats 030104 developmental biology medicine.anatomical_structure Endocrinology chemistry Molecular Medicine lipids (amino acids peptides and proteins) Lysophospholipids Propionates business 030217 neurology & neurosurgery Gastrointestinal Hepatic Pulmonary and Renal Kidney disease |
| Zdroj: | J Pharmacol Exp Ther |
| ISSN: | 1521-0103 |
| Popis: | Lysophosphatidic acid (LPA) is a bioactive lipid mediator that has been implicated in the pathophysiology of kidney disease. However, few studies have attempted to measure changes in the levels of various LPA species in the kidney following the development of renal disease. The present study measured the renal LPA levels during the development of kidney disease in rat models of hypertension, diabetes, and obstructive nephropathy, using liquid chromatography/mass spectrometry/mass spectrometry (LC/MS/MS). LPA levels (sum of 16:0, 18:0, 18:1, 18:2, and 20:4 LPA) were higher in the renal cortex of hypertensive Dahl salt-sensitive (Dahl S) rats fed a high salt diet than in normotensive rats fed a low salt diet (296.6 {plus minus} 22.9 versus 196.3 {plus minus} 8.5 nmol/g protein). LPA levels were elevated in the outer medulla of the kidney of streptozotocin-induced type 1 diabetic Dahl S rats compared with control rats (624.6 {plus minus} 129.5 versus 318.8 {plus minus} 17.1 nmol/g protein). LPA levels were also higher in the renal cortex of 18-month-old, type 2 diabetic nephropathy (T2DN) rats with more severe renal injury than in 6-month-old T2DN rats (184.9 {plus minus} 20.9 versus 116.9 {plus minus} 6.0 nmol/g protein). LPA levels also paralleled the progression of renal fibrosis in the renal cortex of SD rats following unilateral ureteral obstruction (UUO). Administration of a LPA receptor antagonist, Ki16425, reduced the degree of renal fibrosis in UUO rats. These results suggest that the production of renal LPA increases during the development of renal injury and contribute to renal fibrosis. Significance Statement The present study reveals that the LPA levels increase in the kidney in rat models of hypertension, diabetes, and obstructive nephropathy and administration of a LPA receptor antagonist attenuates renal fibrosis. Therapeutic approaches that target the formation or actions of renal LPA might be renoprotective and have therapeutic potential. |
| Databáze: | OpenAIRE |
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