Journal of Shanghai Jiao Tong University (Medical Science) >

2021 , Vol. 41 >Issue 10: 1290 - 1296

DOI: https://doi.org/10.3969/j.issn.1674-8115.2021.10.003

Basic research

Relation of down-regulation of METTL10 and podocyte injury

  • Ji-wen BAO ,
  • Zi-yang LI ,
  • Huan-zhen YAO ,
  • Bei WU ,
  • Wen-yan ZHOU ,
  • Le-yi GU ,
  • Ling WANG
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  • Department of Nephrology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China
WANG Ling, E-mail: shwangling@126.com.

Online published: 2021-09-22

Supported by

Natural Science Foundation of Shanghai(19ZR1430800)

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Abstract

Objective

·To identify the differentially expressed genes (DEGs) in podocyte injury and validate the expression of METTL10, one of these critical genes.

Methods

·The microarray expression profile of a podocyte injury model, dataset GSE108629, was downloaded from the GEO database, containing 4 normal podocyte samples and 4 injured podocyte samples, and the DEGs were diagnosed using the limma software package and affy software package (|log FC| ≥ 2 and adjusted P value<0.05). Patients with significant proteinuria who underwent renal biopsy and were diagnosed as focal segmental glomerulosclerosis or minimal change disease were retrospectively enrolled. Control group was patients who underwent renal biopsy and were proven as slight pathological changes or benign arteriolar neophrosclerosis. The general and clinical data were collected, and the expression of METTL10 in renal tissue was detected by immunofluorescence staining. Adriamycin (ADR)-induced nephropathy mouse model was established by a single intravenous injection of ADR into BAL/BC mouse. Mice were randomly divided into two groups: control group (treated with the same volume of PBS) and ADR group (treated with ADR 10 mg/kg body weight). On Day 0 and Day 14, urine was collected for 24 h using a metabolic cage and urinary albumin creatinine ratio (UACR) of mice were detected; on Day 15, mice were sacrificed and kidney tissue was collected. The expression of METTL10 and podocyte marker proteins like synaptopodin, nephrin, podocin, and Wilms' tumor 1 (WT1) in kidneys from ADR-treated mouse model was analyzed by Western blotting.

Results

·A total of 5 353 genes were significantly differentially expressed in injured podocytes compared with intact podocytes, among which 3 402 DEGs were up-regulated and 1 951 DEGs were down-regulated. METTL10 was found to be one of those that overe significantly down-regulated. Immunofluorescence staining indicated that METTL10 was expressed in normal human glomeruli and METTL10 was colocalized with podocalyxin, one of podocyte specific markers. Additionally, METTL10 was low expressed in the renal biopsy specimens from patients with significant proteinuria compared with that in the control group. On Day 14 after administration of ADR, mice developed significant proteinuria, shown by UACR detection (P=0.005); Western blotting revealed that METTL10 was significantly down-regulated (P=0.001), along with the significantly decreased expression of synaptopodin (P=0.001), nephrin (P=0.005), podocin (P=0.000) and WT1 (P=0.006) in ADR-treated mice compared with that in normal mice. The differences of the expression of METTL10 and the above podocyte markers between these two groups were statistically significant.

Conclusion

·The down-regulation of METTL10 may be involved in podocyte injury.

Key words： podocyte injury; proteinuria; METTL10; differentially expressed genes (DEGs)

Cite this article

Ji-wen BAO , Zi-yang LI , Huan-zhen YAO , Bei WU , Wen-yan ZHOU , Le-yi GU , Ling WANG . Relation of down-regulation of METTL10 and podocyte injury[J]. Journal of Shanghai Jiao Tong University (Medical Science), 2021 , 41(10) : 1290 -1296 . DOI: 10.3969/j.issn.1674-8115.2021.10.003

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