Abstract:
:Although fibronectin (FN) modified by advanced glycation end products (AGEs) has been shown to contribute to the development of diabetic vascular complications through its reduced adhesive activity to vascular cells, little is known about changes in the cell binding domain of AGE-modified FN. Here we examined the mechanism of reduced adhesive and spreading activities of AGE-modified FN to vascular smooth muscle cells (SMCs), particularly the contribution of modification of Arg-Gly-Asp (RGD) sequence. Incubation with glucose caused not only the formation of N(epsilon) -carboxymethyllysine and pentosidine, but also polymerization of FN in a dose- and time-dependent manner. AGE-modified FN had significantly low adhesive and spreading activities to cultured SMCs. On the other hand, multimeric FN formed by disulfide bonds did not show any effect on either cell adhesion or spreading. The adhesive activity of type I collagen, one of the RGD sequence-containing proteins, to SMCs also decreased by AGE-modification. The inhibitory effect of AGE-modification on cell adhesion was significantly greater in type I collagen than in FN. Although the extent of AGE-modification of type I collagen was indistinguishable from that of FN, AGE-modification decreased the arginine content of type I collagen by 69.5% and of FN by 30.6%, compared with their non-glycated forms. The addition of RGD peptides caused a decrease in adhesion of SMCs to non-glycated FN, but not to AGE-modified FN. Modification of RGD sequence with glyoxal eliminated its inhibitory effect on cell adhesion. Our results suggest that a marked decrease in adhesive and spreading activities of AGE-modified FN to SMCs might largely be due to a modification of its RGD sequence by AGE, thus suggesting a potential link between AGE modification of FN and the pathogenesis of diabetic angiopathy.
journal_name
Connect Tissue Resjournal_title
Connective tissue researchauthors
Sakata N,Sasatomi Y,Meng J,Ando S,Uesugi N,Takebayashi S,Nagai R,Horiuchi Sdoi
10.3109/03008200009005291keywords:
subject
Has Abstractpub_date
2000-01-01 00:00:00pages
213-28issue
3eissn
0300-8207issn
1607-8438pii
I120J001005journal_volume
41pub_type
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journal_title:Connective tissue research
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更新日期:1996-01-01 00:00:00
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journal_title:Connective tissue research
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更新日期:2019-05-01 00:00:00
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更新日期:2006-01-01 00:00:00
abstract::The effect of intra-bone injection of differentiated rat bone marrow mesenchymal stem cells (BMMSCs) into the femur of osteoporotic female rats was studied. Osteoporosis was induced in Wistar female rats by bilateral ovariectomy. Then, 0.75 million BMMSCs isolated from healthy rats were injected into the femurs of ost...
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更新日期:2010-12-01 00:00:00
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journal_title:Connective tissue research
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更新日期:1995-01-01 00:00:00
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journal_title:Connective tissue research
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doi:10.3109/03008209109152168
更新日期:1991-01-01 00:00:00
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journal_title:Connective tissue research
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doi:
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journal_title:Connective tissue research
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journal_title:Connective tissue research
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journal_title:Connective tissue research
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更新日期:1982-01-01 00:00:00
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journal_title:Connective tissue research
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更新日期:1988-01-01 00:00:00
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journal_title:Connective tissue research
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更新日期:1996-01-01 00:00:00
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journal_title:Connective tissue research
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