Elevated ALOX12 in renal tissue predicts progression in diabetic kidney disease

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.

Keywords:

• Diabetic kidney disease
• ALOX12
• bioinformatics
• transcriptome

Author contributions

MXW conceived the study, conducted the experiments, and drafted the manuscript. JJW acquired and analyzed the data, MXW and JJW analyzed and interpreted the data, JNW designed and interpreted the study, and XMQ and YGW reviewed and edited the manuscript and participated in the writing of revisions to the manuscript.

Ethical approval

The First Affiliated Hospital of Anhui Medical University's Medical Ethics Committee approved the trial (PJ2022-13-10).

Consent form

Not applicable.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

The datasets used and/or analyzed during the present study are available from the corresponding author on reasonable request.

Additional information

Funding

This work acknowledges the support of the National Natural Science Foundation of China (82070750).