scholarly journals Insulin-like Growth Factor I (IGF-I) Induces Unique Effects in the Cytoskeleton of Cultured Rat Glomerular Mesangial Cells

1997 ◽  
Vol 45 (4) ◽  
pp. 583-593 ◽  
Author(s):  
Anne K. Berfield ◽  
Douglas Spicer ◽  
Christine K. Abrass

Resident glomerular mesangial cells (MCs) have complex cytoskeletal organizations that maintain functional and structural integrity. The ability of cells to replicate, coordinate movement, change shape, and interact with contiguous cells or extracellular matrix depends on cytoskeletal organization. MCs synthesize insulin-like growth factor (IGF-I), express IGF-I receptors, and respond to IGF-I with increased proliferation. We noted that IGF-I treatment of mesangial cells was associated with a change in morphology. Therefore, these studies were undertaken to define specific IGF-I-mediated changes in cytoskeletal protein organization. Rat MCs were propagated from birth in culture without supplemental insulin. Quiescent, subconfluent cultures were treated with IGF-I (100 nM) for 1 hr. Rearrangements in f-actin, α-smooth muscle actin, β-actin, vimentin, and vinculin were seen by fluorescence microscopy. As the cytoskeleton rearranged, α-smooth muscle actin dissociated from the f-actin bundles and β-actin became polymerized under the leading lamellar edge. Ultrastructural changes were consistent with increased membrane turnover and metabolic activity. The normally sessile mesangial cell was induced by IGF-I to express a wound-healing phenotype characterized by movement and increased pinocytosis. These changes are different from those induced by insulin and have important implications for mesangial cell function.

1996 ◽  
Vol 270 (4) ◽  
pp. F614-F622 ◽  
Author(s):  
M. Kitamura ◽  
T. Mitarai ◽  
R. Nagasawa ◽  
N. Maruyama

Prolonged culture of glomerular mesangial cells forms nodular structures composed of cells and surrounding extracellular matrix (ECM), which may mimic the situation in the glomerular mesangium of the kidney. The aim of this study was to investigate whether nodule-associated cells (NAC) exhibit a different phenotype to nodule-unassociated cells (NUC) in vitro. As phenotypic markers for rat mesangial cells, we examined mitogenic activity, expression of alpha-smooth muscle actin, and production of ECM constituents. Autoradiographic and immunohistochemical analyses revealed that NAC showed far less mitogenesis that NUC, like mesangial cells in the normal glomerulus. Immunofluorescence study and Northern blot analysis showed that alpha-smooth muscle actin, a marker of mesangial cell activation/dedifferentiation, was strongly expressed in NUC but faint in NAC. When nodules were dissolved by trypsinization, the dispersed NAC regained both active mitogenesis and alpha-smooth muscle actin expression, suggesting that the altered phenotype was reversible. Northern blot analysis revealed that the ratio of type IV collagen versus type I collagen expression, a marker of mesangial cell differentiation, was elevated in NAC compared with NUC. This phenotypic shift toward differentiation was associated with upregulation of transforming growth factor-beta 1. These findings demonstrate that mesangial cells in nodules exhibit a phenotype which is distinct from that of cells in two-dimensional cultures. We hypothesize that, as a differentiated feature, cultured mesangial cells have the ability to create an appropriate three-dimensional cyto-architecture that resembles the glomerular mesangium.


1997 ◽  
Vol 273 (6) ◽  
pp. F899-F906 ◽  
Author(s):  
Christine K. Abrass ◽  
Anne K. Berfield ◽  
Dennis L. Andress

Insulin-like growth factor I (IGF-I) binding protein-5 (IGFBP-5) is produced by mesangial cells (MCs) and likely functions to modulate glomerular IGF-I activity. Although IGFBP-5 may be inhibitory for IGF-stimulated MC activity, preliminary studies suggested that IGFBP-5 acts directly on MCs. To investigate this further, we evaluated the effects of IGFBP-5 on rat MC migration. We found that the carboxy-truncated fragment, IGFBP-5-(1–169), inhibited IGF-I-stimulated migration, but intact IGFBP-5 simulated migration when IGF-I was not present. Demonstration that125I-labeled IGFBP-5 directly binds to MCs further supports an independent role for IGFBP-5. Because heparin inhibited MC binding of125I-IGFBP-5, we tested the heparin binding peptide, IGFBP-5-(201–218), for stimulatory activity. IGFBP-5-(201–218) stimulated MC migration, and this effect was inhibited by heparin. Because the disintegrin, kistrin, blocked IGF-I-induced migration but not migration induced by IGFBP-5-(201–218), the migratory induction mechanism for the two peptides is different. These data indicate that separate, specific regions of IGFBP-5 are responsible for interactive effects with IGF-I as well as direct effects on MC activity.


1991 ◽  
Vol 5 (2-3) ◽  
pp. 184-185 ◽  
Author(s):  
Masaki Togawa ◽  
Ryuichi Kikkawa ◽  
Masakazu Haneda ◽  
Daisuke Koya ◽  
Naoki Horide ◽  
...  

1988 ◽  
Vol 255 (6) ◽  
pp. F1214-F1219 ◽  
Author(s):  
F. G. Conti ◽  
L. J. Striker ◽  
S. J. Elliot ◽  
D. Andreani ◽  
G. E. Striker

Mesangial cell proliferation is a common hallmark of many glomerular diseases. The exact mechanisms inducing cell proliferation in glomerulosclerosis are not completely understood, and it remains to be determined whether growth factors play a role in this process. Insulinlike growth factor I (IGF I) has been shown to be synthesized in the kidney, and glomerular mesangial cells have receptors for and exhibit mitogenic response to IGF I. We found that mouse glomerular mesangial cells in culture synthesized and released into the culture medium a molecule with immunological and biological features of IGF I. This molecule specifically bound to mesangial cell IGF I receptors; high-pressure liquid chromatographic analysis provided further evidence of its similarity to human recombinant IGF I. Mesangial cells released into the culture medium 6 ng/10(6) cells of IGF I-like material per 24 h in a time-dependent and actinomycin-D inhibitable fashion. These data suggest that IGF I might be locally released by mesangial cells in the glomerulus and act in an autocrine and paracrine fashion.


Endocrinology ◽  
1988 ◽  
Vol 122 (6) ◽  
pp. 2788-2795 ◽  
Author(s):  
FRANCESCO G. CONTI ◽  
LILIANE J. STRIKER ◽  
MAXINE A. LESNIAK ◽  
KAREN MACKAY ◽  
JESSE ROTH ◽  
...  

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