Mechanisms and kinetics of Bowman's epithelial-myofibroblast transdifferentiation in the formation of glomerular crescents.
BACKGROUND
We investigated the mechanisms and kinetics of Bowman's epithelial-myofibroblast transdifferentiation in the formation of glomerular crescents.


METHODS
Crescentic glomerulonephritis was induced by i.v. injection of rabbit anti-rat glomerular basement membrane antiserum in WKY rats.


RESULTS
Cellular crescents (83.5% of glomeruli) were first observed at day 7 after disease induction. Immunostaining of alpha-smooth muscle actin (alpha-SMA), as a marker for the myofibroblast phenotype, was found in some periglomerular regions as early as day 3, when it was also seen in parietal epithelial cells (PEC) of Bowman's capsule at day 5 and in crescent formation at day 7. Proliferation marker Ki67-positive PEC was found at day 3, and double Ki67- and alpha-SMA-positive PEC could be seen at day 5. The migratory figure of PEC with the expression of alpha-SMA was found by immunoelectron microscopy. At day 7, some crescent cells were stained positive for PEC marker, protein gene product 9.5, in association with alpha-SMA or Ki67. Expression of transforming growth factor (TGF)-beta receptor types I and II, as well as platelet-derived growth factor (PDGF) receptor beta and PDGF-B increased in PEC as early as day 3. At day 5 marked deposition of cellular and common fibronectin, but not other extracellular matrix components examined was found in Bowman's spaces where ED 1-positive macrophages infiltrated.


CONCLUSIONS
PEC may be stimulated to proliferate and/or transdifferentiate into myofibroblast phenotype possibly by action of TGF-beta and PDGF and/or binding of fibronectin to PEC, then migrate and/or proliferate, participating in glomerular crescents.
First Department of Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan. yf0516@hama-med.ac.jp
Yoshihide
Y
Fujigaki
Di Fei
DF
Sun
Taiki
T
Fujimoto
Takayuki
T
Suzuki
Tetsuo
T
Goto
Katsuhiko
K
Yonemura
Tetsuo
T
Morioka
Eishin
E
Yaoita
Akira
A
Hishida
D030201:Activin Receptors, Type I / Q000032:analysis; D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D001323:Autoantibodies; D002454:Cell Differentiation; D004847:Epithelial Cells / Q000473:pathology*; D005109:Extracellular Matrix / Q000473:pathology; D005347:Fibroblasts / Q000473:pathology*; D005921:Glomerulonephritis / Q000276:immunology / Q000473:pathology*; D007678:Kidney Glomerulus / Q000737:chemistry / Q000473:pathology*; D007700:Kinetics; D008264:Macrophages / Q000276:immunology / Q000473:pathology; D008297:Male; D017346:Protein Serine-Threonine Kinases; D020574:Proto-Oncogene Proteins c-sis / Q000032:analysis; D051381:Rats; D011921:Rats, Inbred WKY; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000032:analysis; D000077293:Receptor, Transforming Growth Factor-beta Type I; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000032:analysis
D000906:Antibodies; D001323:Autoantibodies; D020574:Proto-Oncogene Proteins c-sis; D018125:Receptors, Transforming Growth Factor beta; C051951:antiglomerular basement membrane antibody; D020797:Receptor, Platelet-Derived Growth Factor beta; D017346:Protein Serine-Threonine Kinases; D030201:Activin Receptors, Type I; D000077293:Receptor, Transforming Growth Factor-beta Type I; D000077294:Receptor, Transforming Growth Factor-beta Type II; C000625843:Tgfbr1 protein, rat