Analysis of glial cell line-derived neurotrophic factor-inducible zinc finger protein 1 expression in human diseased kidney

Shoji Saito, Yoshiki Murakumo, Toyonori Tsuzuki, Atsushi Dambara, Takuya Kato, Atsushi Enomoto, Naoya Asai, Shoichi Maruyama, Seiichi Matsuo, Masahide Takahashi

Research output: Contribution to journalArticlepeer-review

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Abstract

The glial cell line-derived neurotrophic factor (GDNF)-RET signaling pathway plays an important role in kidney development. We have previously identified a novel zinc finger protein, glial cell line-derived neurotrophic factor-inducible zinc finger protein 1 (GZF1), whose expression was induced in the human neuroblastoma cell line TGW expressing RET by GDNF stimulation and was also detected in mouse metanephric kidney. In the present study, we examined the immunohistochemical expression of GZF1 in normal human kidney and various kidney diseases including chronic kidney disease, acute kidney injury, and cancers, and assessed the clinical significance of GZF1 expression. In the normal kidney, GZF1 was highly expressed only in the proximal tubular epithelial cells that were also positive for angiotensin-converting enzyme. We also evaluated GZF1 expression in various kidney diseases including membranous nephropathy, minimal change nephrotic syndrome with or without acute kidney injury, immunoglobulin A nephropathy, diabetic nephropathy, acute tubular necrosis, and antineutrophil cytoplasmic antibody-related glomerulonephritis. We found that decreased expression of GZF1 was associated with an increase in tubulointerstitial damage and serum creatinine levels. In addition, GZF1 expression was undetectable or very low in most cases of renal cell carcinomas and Wilms tumors. These findings suggest that GZF1 represents a new marker for renal proximal tubules and that there is an inverse correlation between the expression level of GZF1 and tubular function.

Original languageEnglish
Pages (from-to)848-858
Number of pages11
JournalHuman Pathology
Volume42
Issue number6
DOIs
Publication statusPublished - 06-2011
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Pathology and Forensic Medicine

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