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Heparin binding domain of insulin-like growth factor binding protein-5 stimulates mesangial cell migration
C K Abrass1, A K Berfield, D L Andress
1Department of Medicine, Department of Veterans Affairs Puget Sound Health Care System, Seattle, Washington, USA.
Abstract:
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 carboxytruncated fragment, IGFBP-5-(1-169), inhibited IGF-I-stimulated migration, but intact IGFBP-5 simulated migration when IGF-I was not present. Demonstration that 125I-labeled IGFBP-5 directly binds to MCs further supports an independent role for IGFBP-5. Because heparin inhibited MC binding of 125I-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.
Insights
Insulin-like growth factor I binding protein-5 (IGFBP-5) directly influences mesangial cell migration. Specific regions of IGFBP-5 mediate distinct interactions with IGF-I and direct cellular effects, revealing a dual role in kidney cell activity.
Area of Science:
- Nephrology
- Cell Biology
- Biochemistry
Background:
- Insulin-like growth factor I (IGF-I) binding protein-5 (IGFBP-5) is produced by mesangial cells (MCs).
- IGFBP-5's role in modulating glomerular IGF-I activity and its direct effects on MCs are not fully understood.
Purpose of the Study:
- To investigate the direct effects of IGFBP-5 on rat mesangial cell (MC) migration.
- To determine the specific regions of IGFBP-5 responsible for its interactions with IGF-I and direct MC activity.
Main Methods:
- Evaluated the effects of intact IGFBP-5 and its fragments (IGFBP-5-(1-169), IGFBP-5-(201-218)) on rat MC migration.
- Utilized 125I-labeled IGFBP-5 to assess direct binding to MCs.
- Investigated the role of heparin and kistrin in modulating IGFBP-5-induced migration.
Main Results:
- Intact IGFBP-5 stimulated MC migration independently of IGF-I, while the carboxy-truncated fragment IGFBP-5-(1-169) inhibited IGF-I-stimulated migration.
- 125I-labeled IGFBP-5 directly bound to MCs, confirming an independent role.
- The heparin-binding peptide IGFBP-5-(201-218) stimulated MC migration, an effect inhibited by heparin.
- Kistrin blocked IGF-I-induced migration but not migration induced by IGFBP-5-(201-218), indicating different mechanisms.
Conclusions:
- Separate regions of IGFBP-5 mediate distinct functions: interaction with IGF-I and direct stimulation of MC migration.
- IGFBP-5 possesses a dual role, influencing both IGF-I activity and directly modulating mesangial cell behavior.