Disruption of the hyaluronan-based extracellular matrix in spinal cord promotes astrocyte proliferation.
Astrocyte proliferation is tightly controlled during development and in the adult nervous system. In the present study, we find that a high-molecular-weight (MW) form of the glycosaminoglycan hyaluronan (HA) is found in rat spinal cord tissue and becomes degraded soon after traumatic spinal cord injury. Newly synthesized HA accumulates in injured spinal cord as gliosis proceeds, such that high-MW HA becomes overabundant in the extracellular matrix surrounding glial scars after 1 month. Injection of hyaluronidase, which degrades HA, into normal spinal cord tissue results in increased numbers of glial fibrillary acidic protein (GFAP)-positive cells that also express the nuclear proliferation marker Ki-67, suggesting that HA degradation promotes astrocyte proliferation. In agreement with this observation, adding high- but not low-MW HA to proliferating astrocytes in vitro inhibits cell growth, while treating confluent, quiescent astrocyte cultures with hyaluronidase induces astrocyte proliferation. Collectively, these data indicate that high-MW HA maintains astrocytes in a state of quiescence, and that degradation of HA following CNS injury relieves growth inhibition, resulting in increased astrocyte proliferation.
Struve
Jaime
J
Division of Neuroscience, Oregon National Primate Research Center, Oregon Health and Science University, Beaverton, Oregon, USA.
Maher
P Colby
PC
Li
Ya-Qin
YQ
Kinney
Shawn
S
Fehlings
Michael G
MG
Kuntz
Charles
C
Sherman
Larry S
LS
D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000378:metabolism*; D049109:Cell Proliferation; D002478:Cells, Cultured; D002921:Cicatrix / Q000378:metabolism / Q000503:physiopathology; D004195:Disease Models, Animal; D005109:Extracellular Matrix / Q000378:metabolism*; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000187:drug effects / Q000378:metabolism; D005911:Gliosis / Q000378:metabolism* / Q000503:physiopathology; D006820:Hyaluronic Acid / Q000378:metabolism*; D006821:Hyaluronoglucosaminidase / Q000378:metabolism / Q000494:pharmacology; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000378:metabolism; D008970:Molecular Weight; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000166:cytology / Q000378:metabolism* / Q000503:physiopathology; D013117:Spinal Cord Compression / Q000378:metabolism* / Q000503:physiopathology; D015854:Up-Regulation / Q000502:physiology
D005904:Glial Fibrillary Acidic Protein; D019394:Ki-67 Antigen; D006820:Hyaluronic Acid; D006821:Hyaluronoglucosaminidase