Regeneration-associated high level expression of apolipoprotein D mRNA in endoneurial fibroblasts of peripheral nerve.

Abstract

A cDNA clone containing the entire coding region of rat apolipoprotein D (Apo D) was isolated from a cDNA library of regenerating sciatic nerve by differential hybridization. Only small amounts of Apo D mRNA were detected in noninjured mature nerve. Moderately increased levels of Apo D transcripts were found in transected nerves, which were prevented from regeneration by ligation. In contrast, in regenerating crushed nerve, the steady‐state level of Apo D mRNA transiently increased at least 40‐fold above control levels at the time when axons from the proximal stump grow into the distal nerve segment. Using transverse sections and primary cell cultures from regenerating nerve, Apo D transcripts could be localized by in situ hybridization in endoneurial fibroblasts but not in Schwann cells, macrophages or perineurial and epineurial cells. Apo D protein (Mr 32.8 kd) was secreted and accumulated in the endoneurial extracellular space where it could be detected in lipoprotein fractions by immunoblotting using established antibodies to human Apo D. High level expression of Apo D mRNA seems to be a novel regeneration‐associated molecular event of endoneurial fibroblasts indicating a function for Apo D and fibroblasts in nerve repair.

Apolipoprotein D is Elevated in Oligodendrocytes in the Peri-Infarct Region after Experimental Stroke: Influence of Enriched Environment

“…We also found that after MCAO, apoD levels increase in the white matter and in the peri-infarct areas at 2 days of recovery, in line with our earlier in situ hybridization findings from experiments using a tMCAO model (Rickhag et al, 2006). After peripheral nerve injury, apoD levels increase significantly in regenerating areas and likely contribute to nerve regeneration (Spreyer et al, 1990). During rat brain development, enhanced expression of apoD coincides with the period of active myelination (Ong et al, 1999).…”

The lipocalin protein family: structure and function

“…Boyles et al [123] and Spreyer et al [124] both report a correlation between increased apoD expression and nerve regeneration consistent with the protein acting in the repair process. Boyles et al report a 500-fold increase in apoD expression in regenerating rat, rabbit and marmoset peripheral nerves.…”

Apolipoprotein D transcription occurs specifically in nonproliferating quiescent and senescent fibroblast cultures

“…We could postulate that apoD plays a role in cellular homeostasis, required only under some metabolic conditions that occur following growth arrest, or that expression of apoD is a marker of the induction of fibroblasts into a particular functional state. The finding of high levels of apoD mRNA and protein in endoneurial fibroblasts during nerve regeneration [19,20] fsvours the hypothesis that exogenous factors may induce the expression of apoD and that fibroblasts that express it have developed a new function or activity.…”