Evidence for distinct leptomeningeal cell-dependent paracrine and EGF-linked autocrine regulatory pathways for suppression of fibrillar collagens in astrocytes.
A unique and unresolved property of the central nervous system is that its extracellular matrix lacks fibrillar elements. In the present report, we show that astrocytes secrete triple helices of fibrillar collagens type I, III and V in culture, while no astroglial collagen expression could be detected in vivo. We discovered two inhibitory mechanisms that could underlie this apparent discrepancy. Thus, we uncover a strong inhibitory effect of meningeal cells on astrocytic collagen expression in coculture assays. Furthermore, we present evidence that EGF-receptor activation downregulates collagen expression in astrocytes via an autocrine loop. These investigations provide a rational framework to explain why the brain is devoid of collagen fibers, which is a unique feature that characterizes the structure of the neural extracellular matrix. Moreover, fibrillar collagens were found transiently upregulated in a laser-induced cortical lesion, suggesting that these could contribute to the glial scar that inhibits axonal regeneration.
Heck
Nicolas
N
Centre de Neurochimie, CNRS, 67084, Strasbourg Cedex, France.
Garwood
Jeremy
J
Dobbertin
Alexandre
A
Calco
Valérie
V
Sirko
Swetlana
S
Mittmann
Thomas
T
Eysel
Ulf T
UT
Faissner
Andreas
A
D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000187:drug effects* / Q000378:metabolism / Q000528:radiation effects; D019898:Autocrine Communication / Q000502:physiology*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D018920:Coculture Techniques / Q000379:methods; D017077:Culture Media, Conditioned / Q000494:pharmacology; D016207:Cytokines / Q000494:pharmacology; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D024022:Fibrillar Collagens / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects* / Q000502:physiology; D007834:Lasers / Q000009:adverse effects; D008578:Meninges / Q000166:cytology*; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D020032:Tyrphostins / Q000494:pharmacology
D017077:Culture Media, Conditioned; D016207:Cytokines; D024022:Fibrillar Collagens; D012333:RNA, Messenger; D020032:Tyrphostins; C086599:tyrphostin A46; D004815:Epidermal Growth Factor