title: Development of lymphatic vasculature and morphological characterization in rat kidney.
abstract: BACKGROUND
  The mechanisms and morphological characteristics of lymphatic vascular development in embryonic kidneys remain uncertain.
  
  
  METHODS
  We examined the distribution and characteristics of lymphatic vessels in developing rat kidneys using immunostaining for podoplanin, prox-1, Ki-67, type IV collagen (basement membrane: BM), and α-smooth muscle actin (αSMA: pericytes or mural cells). We also examined the expression of VEGF-C.
  
  
  RESULTS
  At embryonic day 17 (E17), podoplanin-positive lymphatic vessels were observed mainly in the kidney hilus. At E20, lymphatic vessels extended further into the developing kidneys along the interlobar vasculature. In 1-day-old pups (P1) to P20, lymphatic vessels appeared around the arcuate arteries and veins of the kidneys, with some reaching the developing cortex via interlobular vessels. In 8-week-old adult rats, lymphatic vessels were extensively distributed around the blood vasculature from the renal hilus to cortex. Only lymphatic capillaries lacking continuous BM and αSMA-positive cells were present within adult kidneys, with none observed in renal medulla. VEGF-C was upregulated in the developing kidneys and expressed mainly in tubules. Importantly, the developing lymphatic vessels were characterized by endothelial cells immunopositive for podoplanin, prox-1, and Ki-67, with no surrounding BM or αSMA-positive cells.
  
  
  CONCLUSIONS
  During nephrogenesis, lymphatic vessels extend from the renal hilus into the renal cortex along the renal blood vasculature. Podoplanin, prox-1, Ki-67, type IV collagen, and αSMA immunostaining can detect lymphatic vessels during lymphangiogenesis.
authors.affiliation: Department of Analytic Human Pathology, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo 113-8602, Japan.
authors.forename: Maki
authors.initials: M
authors.lastname: Tanabe
authors.forename: Akira
authors.initials: A
authors.lastname: Shimizu
authors.forename: Yukinari
authors.initials: Y
authors.lastname: Masuda
authors.forename: Mitue
authors.initials: M
authors.lastname: Kataoka
authors.forename: Arimi
authors.initials: A
authors.lastname: Ishikawa
authors.forename: Kyoko
authors.initials: K
authors.lastname: Wakamatsu
authors.forename: Akiko
authors.initials: A
authors.lastname: Mii
authors.forename: Emiko
authors.initials: E
authors.lastname: Fujita
authors.forename: Seiichiro
authors.initials: S
authors.lastname: Higo
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Kaneko
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kawachi
authors.forename: Yuh
authors.initials: Y
authors.lastname: Fukuda
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D049109:Cell Proliferation; D024141:Collagen Type IV / Q000378:metabolism; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism; D018398:Homeodomain Proteins / Q000378:metabolism; D019394:Ki-67 Antigen / Q000378:metabolism; D007668:Kidney / Q000033:anatomy & histology / Q000196:embryology* / Q000254:growth & development*; D042583:Lymphangiogenesis / Q000502:physiology*; D042601:Lymphatic Vessels / Q000166:cytology* / Q000196:embryology* / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000378:metabolism; D023421:Models, Animal; D009024:Morphogenesis / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D025521:Tumor Suppressor Proteins / Q000378:metabolism; D042582:Vascular Endothelial Growth Factor C / Q000378:metabolism; D000098551:Prospero-Related Homeobox 1 Protein; D000098853:Podoplanin
chemical_list: D000199:Actins; D024141:Collagen Type IV; D018398:Homeodomain Proteins; D019394:Ki-67 Antigen; D008562:Membrane Glycoproteins; D025521:Tumor Suppressor Proteins; D042582:Vascular Endothelial Growth Factor C; D000098551:Prospero-Related Homeobox 1 Protein; C092025:Pdpn protein, rat; D000098853:Podoplanin; C498862:Acta2 protein, rat