» Articles » PMID: 38345057

Elevated ALOX12 in Renal Tissue Predicts Progression in Diabetic Kidney Disease

Overview
Journal Ren Fail
Publisher Informa Healthcare
Date 2024 Feb 12
PMID 38345057
Authors
Affiliations
Soon will be listed here.
Abstract

Diabetic kidney disease (DKD) is one of the major causes of end-stage renal disease and one of the significant complications of diabetes. This study aims to identify the main differentially expressed genes in DKD from transcriptome sequencing results and analyze their diagnostic value. The present study sequenced db/m mouse and db/db mouse to determine the ALOX12 genetic changes related to DKD. After preliminary validation, ALOX12 levels were significantly elevated in the blood of DKD patients, but not during disease progression. Moreover, urine ALOX12 was increased only in macroalbuminuria patients. Therefore, to visualize the diagnostic efficacy of ALOX12 on the onset and progression of renal injury in DKD, we collected kidney tissue from patients for immunohistochemical staining. ALOX12 was increased in the kidneys of patients with DKD and was more elevated in macroalbuminuria patients. Clinical chemical and pathological data analysis indicated a correlation between ALOX12 protein expression and renal tubule injury. Further immunofluorescence double staining showed that ALOX12 was expressed in both proximal tubules and distal tubules. Finally, the diagnostic value of the identified gene in the progression of DKD was assessed using receiver operating characteristic (ROC) curve analysis. The area under the curve (AUC) value for ALOX12 in the diagnosis of DKD entering the macroalbuminuria stage was 0.736, suggesting that ALOX12 has good diagnostic efficacy. During the development of DKD, the expression levels of ALOX12 in renal tubules were significantly increased and can be used as one of the predictors of the progression to macroalbuminuria in patients with DKD.

Citing Articles

Lipoxin A improves cardiac remodeling and function in diabetes-associated cardiac dysfunction.

Fu T, Mohan M, Bose M, Brennan E, Kiriazis H, Deo M Cardiovasc Diabetol. 2024; 23(1):413.

PMID: 39563316 PMC: 11577589. DOI: 10.1186/s12933-024-02501-x.

References
1.
Levenson D, Simmons Jr C, Brenner B . Arachidonic acid metabolism, prostaglandins and the kidney. Am J Med. 1982; 72(2):354-74. DOI: 10.1016/0002-9343(82)90826-9. View

2.
Liu Y, Freedman B, Burdon K, Langefeld C, Howard T, Herrington D . Association of arachidonate 12-lipoxygenase genotype variation and glycemic control with albuminuria in type 2 diabetes. Am J Kidney Dis. 2008; 52(2):242-50. PMC: 2585503. DOI: 10.1053/j.ajkd.2007.12.033. View

3.
Kang S, Natarajan R, Shahed A, Nast C, LaPage J, Mundel P . Role of 12-lipoxygenase in the stimulation of p38 mitogen-activated protein kinase and collagen alpha5(IV) in experimental diabetic nephropathy and in glucose-stimulated podocytes. J Am Soc Nephrol. 2003; 14(12):3178-87. DOI: 10.1097/01.asn.0000099702.16315.de. View

4.
Chen W, Zhang X, Bi K, Zhou H, Xu J, Dai Y . Comprehensive Study of Tumor Immune Microenvironment and Relevant Genes in Hepatocellular Carcinoma Identifies Potential Prognostic Significance. Front Oncol. 2020; 10:554165. PMC: 7541903. DOI: 10.3389/fonc.2020.554165. View

5.
Gregus A, Dumlao D, Wei S, Norris P, Catella L, Meyerstein F . Systematic analysis of rat 12/15-lipoxygenase enzymes reveals critical role for spinal eLOX3 hepoxilin synthase activity in inflammatory hyperalgesia. FASEB J. 2013; 27(5):1939-49. PMC: 3633813. DOI: 10.1096/fj.12-217414. View