Expression of Glial Cell Line-Derived Neurotrophic Factor and Neurturin in Mature Kidney, Nephrogenic Rests, and Nephroblastoma: Possible Role as Differentiating Factors

Francesca Diomedi Camassei, Renata Boldrini, Alessandro Jenkner, Alessandro Inserra, Alberto Donfrancesco, Lucilla Rava, Carlo Dominici

Research output: Contribution to journalArticlepeer-review

Abstract

Kidney development involves a series of complex interactions between the ureteric bud and undifferentiated mesenchyme, resulting in the production of the nephron unit. Among locally derived soluble factors, a particular relevance has been recognized to glial cell line-derived neurotrophic factor (GDNF) and neurturin (NTN) for the mesenchyme-to-epithelial conversion of a metanephron. Nephroblastoma is a developmental tumor of the kidney deriving from metanephric blastema that mimics renal development and may offer an adequate model of human nephrogenesis. We investigated the immunohistochemical expression of GDNF, NTN, and their receptors (GFRα1, 2, and 3, and Ret) in normal human kidney and in 42 nephroblastomas, 20 of which were associated with nephrogenic rests (group A) and 22 were not (group B). We compared the immunostaining pattern in group A vs. group B and correlated clinical course with stage, grade, presence of nephrogenic rests, and immunohistochemical findings. GDNF, NTN, and their receptors were expressed in mature kidney and in 67% (GDNF) and 33% (NTN) of tumors, particularly in the epithelial component; precursor lesions were negative. No significant differences of expression were observed between groups A and B tumors. Low stage (P = 0.012), absence of nephrogenic rests (P = 0.016), intense expression of GDNF (P = 0.034), and NTN (P = 0.05) were associated with a more favorable outcome. Besides inductive activity in nephrogenesis, GDNF and NTN may play a role in maintaining differentiation and survival functions in mature kidney and may contribute to induce differentiation of nephroblastoma cells toward the less aggressive epithelial component. The pathway of activation seems to follow an autocrine/paracrine mechanism, as neurotrophic factors, GFRα1-2-3 receptors and Ret are coexpressed.

Original languageEnglish
Pages (from-to)511-519
Number of pages9
JournalPediatric and Developmental Pathology
Volume6
Issue number6
Publication statusPublished - Nov 2003

Keywords

  • GFRα
  • Glial cell line-derived neurotrophic factor
  • Immunohistochemistry
  • Nephroblastoma
  • Nephrogenic rests
  • Neurturin

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Pathology and Forensic Medicine

Fingerprint Dive into the research topics of 'Expression of Glial Cell Line-Derived Neurotrophic Factor and Neurturin in Mature Kidney, Nephrogenic Rests, and Nephroblastoma: Possible Role as Differentiating Factors'. Together they form a unique fingerprint.

Cite this