TY - JOUR
T1 - Modulation of glomerular proteoglycans by insulin-like growth factor-1
AU - Watanabe, Yuzo
AU - Kashihara, Naoki
AU - Makino, Hirofumi
AU - Kanwar, Yashpal S.
N1 - Funding Information:
This research was supported by NIH Grant DK 28492. We thank Dr.
PY - 1992/5
Y1 - 1992/5
N2 - Effect of insulin-like growth factor-1 (IGF) on the synthesis of glomerular proteoglycans (PGs) in an ex vivo recirculating organ perfusion system was investigated. Kidneys were perfused with a medium (∼80 ml) containing [35S]-sulfate (250 μCi/ml) and IGF (62.5 to 625 ng/ml). After radiolabeling, a small cortical piece was saved for tissue autoradiography, and the remaining kidney and the perfusion medium were utilized for biochemical studies. The glomeruli were isolated: their PGs extracted and characterized. A two- to threefold increase of the total radioactivities in tissue and media fractions was observed with the exposure to IGF. By Sepharose CL-6B chromatography, the tissue PGs eluted as two peaks (A and B) with Kav = 0.24 and 0.48, and the majority of the radioactivity was confined to peak A. This peak contained intact PGs while peak B included glycosaminoglycan (GAG) chains. Elution profiles of the glomerular PGs were similar in the control and IGF groups. However, there was a disproportionate increase of chondroitin/dermatan sulfate in the IGF group. The media fractions also had two peaks, and most of the radioactivity was associated with peak B containing GAG chains. A remarkable accentuation of peak B along with significant increase in the chondroitin/ dermatan sulfate were observed in the IGF group. By DEAE-Sephacel chromatography, the PGs/GAGs of IGF group eluted at a relatively lower salt concentration as compared to the control. Autoradiography revealed a relatively high concentration of radioactivity over the mesangium as compared (o the other cell types of the glomerulus. [35S]-methionine studies revealed a generalized increase of protein synthesis in the IGF group, but comparatively much less than that of PGs/GAGs. These results indicate that IGF enhances the biosynthesis of PGs/GAGs by various cell types of the renal glomerulus, especially that of the mesangial cell, as reflected by the selective increase of chondroitin/dermatan sulfate.
AB - Effect of insulin-like growth factor-1 (IGF) on the synthesis of glomerular proteoglycans (PGs) in an ex vivo recirculating organ perfusion system was investigated. Kidneys were perfused with a medium (∼80 ml) containing [35S]-sulfate (250 μCi/ml) and IGF (62.5 to 625 ng/ml). After radiolabeling, a small cortical piece was saved for tissue autoradiography, and the remaining kidney and the perfusion medium were utilized for biochemical studies. The glomeruli were isolated: their PGs extracted and characterized. A two- to threefold increase of the total radioactivities in tissue and media fractions was observed with the exposure to IGF. By Sepharose CL-6B chromatography, the tissue PGs eluted as two peaks (A and B) with Kav = 0.24 and 0.48, and the majority of the radioactivity was confined to peak A. This peak contained intact PGs while peak B included glycosaminoglycan (GAG) chains. Elution profiles of the glomerular PGs were similar in the control and IGF groups. However, there was a disproportionate increase of chondroitin/dermatan sulfate in the IGF group. The media fractions also had two peaks, and most of the radioactivity was associated with peak B containing GAG chains. A remarkable accentuation of peak B along with significant increase in the chondroitin/ dermatan sulfate were observed in the IGF group. By DEAE-Sephacel chromatography, the PGs/GAGs of IGF group eluted at a relatively lower salt concentration as compared to the control. Autoradiography revealed a relatively high concentration of radioactivity over the mesangium as compared (o the other cell types of the glomerulus. [35S]-methionine studies revealed a generalized increase of protein synthesis in the IGF group, but comparatively much less than that of PGs/GAGs. These results indicate that IGF enhances the biosynthesis of PGs/GAGs by various cell types of the renal glomerulus, especially that of the mesangial cell, as reflected by the selective increase of chondroitin/dermatan sulfate.
UR - http://www.scopus.com/inward/record.url?scp=0026537379&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0026537379&partnerID=8YFLogxK
U2 - 10.1038/ki.1992.188
DO - 10.1038/ki.1992.188
M3 - Article
C2 - 1614040
AN - SCOPUS:0026537379
SN - 0085-2538
VL - 41
SP - 1262
EP - 1273
JO - Kidney international
JF - Kidney international
IS - 5
ER -