TY - JOUR
T1 - Fibronectin induces ureteric bud cells branching and cellular cord and tubule formation
AU - Ye, Yeng
AU - Habib, Samy L.
AU - Ricono, Jill M.
AU - Kim, Nam Ho
AU - Choudhury, Goutam G.
AU - Barnes, Jeffrey L.
AU - Abboud, Hanna E.
AU - Arar, Mazen Y.
N1 - Funding Information:
We thank Myrna Gonzales and Maria Bunegin for the technical assistance and Sonia Januario for able secretarial help. This work was supported by Grant-in-Aid, American Heart Association, Texas Affiliate #96G-371 and #97G-439, Fraternal Order of Eagles #70, and Clinical Scientist Award from the National Kidney Foundation (M.A.) and DK33665 (H.E.A.).
PY - 2004/10
Y1 - 2004/10
N2 - Background. The extracellular matrix (ECM) protein fibronectin is involved in several stages of embryogenesis. Fibronectin exerts its effect through interaction with cellular integrin and nonintegrin receptors. Methods. We investigated the effect of fibronectin on branching and tubulogenesis of ureteric bud cells in a three-dimensional gel culture system. Primary ureteric bud cells from mouse embryos at gestation 11 days (E11) were isolated and established in culture. Fibronectin and integrin subunits were localized using immunoperoxidase staining. Results. In three-dimensional collagen type I gel culture of ureteric bud cell, fibronectin dose dependently induces cord and tubule formation. Both ureteric bud cells and ureteric bud branches in embryonic kidney express the same multiple integrin subunits that include β1, β3, α3, α4 and αv. Embryonic kidneys examined at E12, E14, and E16 days of gestation express fibronectin in the undifferentiated mesenchyme especially next to ureteric bud branches and in the interstitium around glomerulotubular structures and blood vessels. Fibronectin expression was similar at the tips and stalks of branching ureteric bud. Fibronectin expression is maximum at E12 and decreases with advanced gestation. Cultured ureteric bud cells also express fibronectin. RGD peptides inhibit cord and tubular formation in the three-dimensional gel. Anti-α3β1 antibody partially inhibits fibronectin-induced cord and tubule formation. Hepatocyte growth factor (HGF), fibroblast growth factor (FGF), and glial cell line-derived neurotrophic factor (GDNF) induce ureteric bud cell cord formation in three-dimensional gel. The effects of growth factors are delayed and quantitatively less compared to the effect of fibronectin. Conclusion. Fibronectin induces ureteric bud cells branching and tubulogenesis through interaction with multiple integrin receptors. Cultured ureteric bud cells express febronectin and the origin of fibronectin at mesenchyme-ureteric bud interface is likely both the metanephric mesenchyme and ureteric bud epithelium. Addition of individual neutralizing antibodies to β1, β3, α3, α4, α6 and αv integrin subunits does not block the effect of fibronectin. Only an antibody to α3β 1 integrin substantially blocks the effect of fibronectin. Other mechanisms, including unidentified integrins, are likely involved in fibronectin-induced cord and tubule formation.
AB - Background. The extracellular matrix (ECM) protein fibronectin is involved in several stages of embryogenesis. Fibronectin exerts its effect through interaction with cellular integrin and nonintegrin receptors. Methods. We investigated the effect of fibronectin on branching and tubulogenesis of ureteric bud cells in a three-dimensional gel culture system. Primary ureteric bud cells from mouse embryos at gestation 11 days (E11) were isolated and established in culture. Fibronectin and integrin subunits were localized using immunoperoxidase staining. Results. In three-dimensional collagen type I gel culture of ureteric bud cell, fibronectin dose dependently induces cord and tubule formation. Both ureteric bud cells and ureteric bud branches in embryonic kidney express the same multiple integrin subunits that include β1, β3, α3, α4 and αv. Embryonic kidneys examined at E12, E14, and E16 days of gestation express fibronectin in the undifferentiated mesenchyme especially next to ureteric bud branches and in the interstitium around glomerulotubular structures and blood vessels. Fibronectin expression was similar at the tips and stalks of branching ureteric bud. Fibronectin expression is maximum at E12 and decreases with advanced gestation. Cultured ureteric bud cells also express fibronectin. RGD peptides inhibit cord and tubular formation in the three-dimensional gel. Anti-α3β1 antibody partially inhibits fibronectin-induced cord and tubule formation. Hepatocyte growth factor (HGF), fibroblast growth factor (FGF), and glial cell line-derived neurotrophic factor (GDNF) induce ureteric bud cell cord formation in three-dimensional gel. The effects of growth factors are delayed and quantitatively less compared to the effect of fibronectin. Conclusion. Fibronectin induces ureteric bud cells branching and tubulogenesis through interaction with multiple integrin receptors. Cultured ureteric bud cells express febronectin and the origin of fibronectin at mesenchyme-ureteric bud interface is likely both the metanephric mesenchyme and ureteric bud epithelium. Addition of individual neutralizing antibodies to β1, β3, α3, α4, α6 and αv integrin subunits does not block the effect of fibronectin. Only an antibody to α3β 1 integrin substantially blocks the effect of fibronectin. Other mechanisms, including unidentified integrins, are likely involved in fibronectin-induced cord and tubule formation.
KW - Extracellular matrix
KW - Integrin receptor
KW - Three-dimensional gel
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U2 - 10.1111/j.1523-1755.2004.00897.x
DO - 10.1111/j.1523-1755.2004.00897.x
M3 - Article
C2 - 15458428
AN - SCOPUS:4644224469
VL - 66
SP - 1356
EP - 1364
JO - Kidney International
JF - Kidney International
SN - 0085-2538
IS - 4
ER -