Activin a produced by ureteric bud is a differentiation factor for metanephric mesenchyme.
The present study was conducted to investigate the role of the activin-follistatin system in the development of metanephros. Organ culture system and cultured metanephric mesenchymal cells were used to address this issue. Activin A was localized in ureteric bud. Activin type II receptor was localized in ureteric bud as well as metanephric mesenchyme. In an organ culture system, exogenous activin A reduced the size of cultured metanephroi, delayed ureteric bud branching, and enlarged the tips of ureteric bud. Follistatin, an antagonist of activin A was used to clarify the role of endogenous activin A. Exogenous follistatin enlarged the size of cultured metanephroi, increased ureteric bud branching, and promoted cell growth in ureteric bud. Blockade of activin signaling by adenoviral transfection of dominantly negative activin mutant receptor mimics the effect of follistatin. In cultured metanephric mesenchymal cells, activin A promoted cell growth; conversely, follistatin induced apoptosis. Furthermore, activin A induced the expressions of epithelial differentiation markers in these cells. These results suggest that activin A produced by ureteric bud is not only an important regulator of ureteric bud branching, but also a differentiation factor for metanephric mesenchyme during kidney development.
Maeshima
Akito
A
Third Department of Internal Medicine, School of Medicine, and Institute for Molecualr and Cellular Regulation, Gunma University, Maebashi, Japan. amaesima@med.gunma-u.ac.jp
Yamashita
Shin
S
Maeshima
Kyoko
K
Kojima
Itaru
I
Nojima
Yoshihisa
Y
D029404:Activin Receptors / Q000235:genetics / Q000378:metabolism; D028341:Activins / Q000096:biosynthesis / Q000494:pharmacology / Q000502:physiology*; D000818:Animals; D000943:Antigens, Differentiation / Q000378:metabolism; D017209:Apoptosis; D002455:Cell Division / Q000187:drug effects; D046508:Culture Techniques; D004268:DNA-Binding Proteins / Q000378:metabolism; D004622:Embryo, Mammalian / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D005314:Embryonic and Fetal Development / Q000502:physiology; D038681:Follistatin / Q000378:metabolism / Q000494:pharmacology; D028322:Inhibin-beta Subunits / Q000096:biosynthesis / Q000494:pharmacology / Q000502:physiology*; D008648:Mesoderm / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D051899:Smad2 Protein; D051900:Smad3 Protein; D014018:Tissue Distribution; D015534:Trans-Activators / Q000378:metabolism; D014162:Transfection; D014513:Ureter / Q000196:embryology*
D000943:Antigens, Differentiation; D004268:DNA-Binding Proteins; D038681:Follistatin; D051899:Smad2 Protein; C497784:Smad2 protein, rat; D051900:Smad3 Protein; C497787:Smad3 protein, rat; D015534:Trans-Activators; C422405:activin A; D028341:Activins; D028322:Inhibin-beta Subunits; D029404:Activin Receptors