Circulating apolipoprotein B-100 promotes scar formation after spinal cord injury

Spinal cord injury (SCI) causes severe neurological dysfunction depending on the neuronal network disruption. Neuronal network regeneration is prevented by the scar tissue formed around the lesion; therefore, inhibition of scar formation is considered to contribute to neuronal network regeneration, resulting in functional recovery. It is known that the scar is composed of several cell types. Among them, recent studies indicated that pericytes act as key players in scarring triggered by their proliferation. Thus, understanding the molecular mechanism regulating pericyte proliferation may be useful to promote neuronal network regeneration after SCI; however, the mechanism is not fully elucidated. Here we focused on the disruption of vascular barrier, a histological feature around the lesion, and found that circulating apolipoprotein B-100 (ApoB-100) promotes pericyte proliferation which contributes to the scar formation after SCI. CRISPR-Cas9 knockout screens with primary mouse pericytes identified that ApoB-100/low-density lipoprotein receptor (LDLR) signal promotes pericyte proliferation. ApoB-100 knockout mice exhibited a decrease in pericyte-derived scar formation and a significant improvement of motor function after SCI. These results suggest that circulating factors, especially ApoB-100, could be a novel therapeutic target for treating SCI.