Spatial and Temporal Changes in the Insulin-Like Growth Factor (IGF) Axis Indicate Autocrine/Paracrine Actions of IGF-I within Wounds of the Rat Brain*
| Autor: | David J. Hill, Ann Logan, Martin Berry, H. J. Walter |
|---|---|
| Rok vydání: | 1997 |
| Předmět: |
medicine.medical_specialty
medicine.medical_treatment Central nervous system In situ hybridization Biology Insulin-like growth factor-binding protein Receptor IGF Type 1 Rats Sprague-Dawley Insulin-like growth factor Paracrine signalling Endocrinology Somatomedins Internal medicine medicine Animals RNA Messenger Insulin-Like Growth Factor I Autocrine signalling In Situ Hybridization Glia limitans Messenger RNA Rats Insulin-Like Growth Factor Binding Proteins Disease Models Animal medicine.anatomical_structure Brain Injuries biology.protein Autoradiography Female hormones hormone substitutes and hormone antagonists |
| Zdroj: | Endocrinology. 138:3024-3034 |
| ISSN: | 1945-7170 0013-7227 |
| DOI: | 10.1210/endo.138.7.5284 |
| Popis: | A precise role for insulin-like growth factors (IGFs), IGF-binding proteins (IGFBPs), and IGF-receptors (IGF-Rs) in damaged central nervous system (CNS) tissue has not been elucidated, although their expression in the ischemic brain has been demonstrated. However, little is known of IGF responses after CNS trauma. In this study, we have used ribonuclease protection assay, in situ hybridization, and immunohistochemistry to demonstrate that IGF-I, IGFBPs, and IGF-1R expression alters in response to a penetrating CNS injury. Within penetrant cerebral wounds in the acute phase of the response (1-7 days post lesion; dpl), increased levels of IGF-I, IGFBP-1, -2, -3, -6, and IGF-1R protein were localized to injury responsive astrocytes, neurons and cells of the monocyte lineage. IGF-I, IGFBP-2, and 3 showed a congruency in sites of messenger RNA (mRNA) and peptide expression, with IGF-I and IGFBP-2 mRNA expression predominating. IGF-I, IGFBP-1, and IGFBP-3 protein were also associated with the microvascular endothelium, which was accompanied by increased levels of IGFBP-3 mRNA. These early changes in IGFBP expression probably facilitate IGF-I action. Later in the wounding response (7-14 dpl), the expression of IGFBP-4 and IGFBP-5 peaked within astrocytes and neurons, with IGFBP-5 mRNA being specifically localized to the glia limitans within the wound, suggesting an inhibitory role for these proteins, down-regulating the effects of IGF-I chronically. Our evidence suggests that within penetrating CNS wounds, IGF-I acts in an autocrine/paracrine manner to regulate cellular responses, with its spatial and temporal availability being modulated by the differential presence of stimulatory vs. inhibitory IGFBPs. |
| Databáze: | OpenAIRE |
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