Evaluation of PGP 9.5, NGFR, TGFβ1, FGFR1, MMP-2, AT2R2, SHH, and TUNEL in Primary Obstructive Megaureter Tissue

J Histochem Cytochem. 2022 Feb;70(2):139-149. doi: 10.1369/00221554211063515. Epub 2021 Dec 17.

Abstract

Primary obstructive megaureter (POM) morphogenesis is not fully known. The aim of the study was to evaluate the appearance of different factors that might take part in the pathogenesis of POM. Megaureter tissues of 14 children were stained with hematoxylin and eosin as well as with immunohistochemistry for protein gene product 9.5, nerve growth factor receptor, transforming growth factor beta 1 (TGFβ1), fibroblast growth factor receptor 1 (FGFR1), matrix metalloproteinase 2 (MMP-2), angiotensin 2 receptor type 2, and sonic hedgehog (SHH) protein. Apoptosis was detected by terminal dUTP nick-end labeling reaction. POM tissues revealed transitional epithelium with scattered vacuolization, submucosa with inflammatory cells, and focally vacuolized and chaotically organized muscle layers. Apoptosis, appearance of MMP-2, FGFR1, and SHH prevailed, but TGFβ1 positive cell number was lower in patients. Correlation between MMP-2 in epithelium and endothelium, FGFR1 and MMP-2 in epithelium, and TGFβ1 in epithelium and connective tissue in patients was detected. POM morphopathogenesis involves an apoptotic cell death of epithelium and smooth muscle as well as tissue degradation in epithelium and connective tissue of the ureter wall. The decrease of tissue growth through diminished TGFβ1 expression and stimulation of FGFR1 and MMP-2 suggests a disbalance of tissue remodelation in the megaureter wall.

Keywords: atrophy; development; growth factors; innervation.

MeSH terms

  • Adolescent
  • Child
  • Child, Preschool
  • Female
  • Hedgehog Proteins / genetics
  • Hedgehog Proteins / metabolism
  • Humans
  • In Situ Nick-End Labeling*
  • Infant
  • Intracellular Signaling Peptides and Proteins / genetics
  • Intracellular Signaling Peptides and Proteins / metabolism
  • LIM Domain Proteins / genetics
  • LIM Domain Proteins / metabolism
  • Male
  • Matrix Metalloproteinase 2 / genetics
  • Matrix Metalloproteinase 2 / metabolism
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism
  • Receptor, Angiotensin, Type 2 / genetics
  • Receptor, Angiotensin, Type 2 / metabolism
  • Receptor, Fibroblast Growth Factor, Type 1 / genetics
  • Receptor, Fibroblast Growth Factor, Type 1 / metabolism
  • Receptors, Nerve Growth Factor / genetics
  • Receptors, Nerve Growth Factor / metabolism
  • Ubiquitin Thiolesterase / genetics
  • Ubiquitin Thiolesterase / metabolism
  • Ureteral Obstruction / genetics*
  • Ureteral Obstruction / metabolism

Substances

  • Hedgehog Proteins
  • Intracellular Signaling Peptides and Proteins
  • LIM Domain Proteins
  • NGFR protein, human
  • Nerve Tissue Proteins
  • Receptor, Angiotensin, Type 2
  • Receptors, Nerve Growth Factor
  • SHH protein, human
  • TGFB1I1 protein, human
  • UCHL1 protein, human
  • FGFR1 protein, human
  • Receptor, Fibroblast Growth Factor, Type 1
  • Ubiquitin Thiolesterase
  • Matrix Metalloproteinase 2