c-kit and ureteral peristalsis

J Urol. 2005 Jan;173(1):292-5. doi: 10.1097/01.ju.0000141594.99139.3d.

Abstract

Purpose: c-kit encodes a tyrosine kinase receptor that is required for the differentiation of a wide variety of cells during embryogenesis, including pacemaker cells of the gut. Functional expression of this tyrosine kinase receptor is required for gut peristalsis and c-kit expression has recently been documented in the adult murine urinary tract. In this study we analyzed the temporal onset of c-kit expression during ureter morphogenesis in vivo and determined if c-kit activity is essential for ureteral peristalsis in vitro.

Materials and methods: The kidneys and ureters of gestational days 12.5 to 17.5 WT mice were isolated and frozen sections were prepared for analysis of c-kit, alpha-smooth muscle actin and uroplakin expression by immunocytochemical techniques. In addition, ureters were isolated from gestational day 15.5 mouse urogenital systems and cultured at the air/medium interface on 0.4 um pore polycarbonate membrane filters with Dulbecco's modified Eagle's medium/fetal calf serum in the presence or absence of antibodies that inhibit c-kit function.

Results: By gestational day 15.5 c-kit expression could be detected in a subset of renal epithelia and cells of the ureteropelvic adventitia. Prominent staining for c-kit was seen in the muscularis propria of the proximal ureter. In vitro studies demonstrated that isolated embryonic ureters acquire the ability to undergo unidirectional contractions after 3 days of culture, which is coincident with up-regulation of c-kit expression. Furthermore, incubation of isolated ureters with antibodies that neutralize c-kit activity markedly altered ureter morphology and peristalsis.

Conclusions: We identified the initial expression and location of c-kit in the embryonic murine upper urinary tract. c-kit expression is up-regulated in the developing ureter prior to the ability of this tissue to undergo unidirectional contractions and c-kit function is required for the peristalsis in vitro.

MeSH terms

  • Animals
  • Immunohistochemistry
  • Mice
  • Muscle Contraction / physiology*
  • Muscle, Smooth / physiology
  • Organ Culture Techniques
  • Proto-Oncogene Proteins c-kit / physiology*
  • Up-Regulation / physiology
  • Ureter / embryology
  • Ureter / metabolism
  • Ureter / physiology*

Substances

  • Proto-Oncogene Proteins c-kit