Abstract
Sushi repeat-containing protein X-linked 2 (SRPX2) is a novel hypothalamic protein and a ligand of the urokinase-type plasminogen activator receptor (uPAR), which is essential for proteolysis of extracellular matrix and tissue remodeling after an insult to the brain. However, little is known about regulation of SRPX2. Our objective was to investigate if SRPX2 expression is altered by (i) the deficiency of uPAR or uPA (urokinase-type plasminogen activator), and (ii) traumatic brain injury (TBI). SRPX2 expression was assessed in wild type (Wt), Plaur-/- (uPAR-deficient), and Plau-/- (uPA-deficient) mice, with and without controlled cortical impact injury (CCI). The number of SRPX2+ neurons in hypothalamus was comparable to that in Wt littermates in Plaur-/- (2985 ± 138 vs. 2890 ± 92, p > 0.05) and Plau-/- mice (2180 ± 232 vs. 2027 ± 77, p > 0.05). The number of hypothalamic SRPX2+ neurons in the Wt-CCI group was comparable to that in controls (3645 ± 288 vs. 3385 ± 192, p > 0.05). Hypothalamic, hippocampal and thalamic Srpx2 gene expression was unaltered after TBI. However, at 4 days post-TBI Srpx2 gene expression was upregulated in the perilesional cortex of Plau-/--CCI mice up to 123% of that in the sham group (p < 0.05). Unsupervised hierarchical clustering using SRPX2 expression did not identify genotype or injury-specific clusters. Our data demonstrate that SRPX2 expression in the hypothalamus is resistant to genetic deficiencies in the urokinase-system or to the hypothalamus-affecting TBI. The contribution of elevated Srpx2 gene expression in perilesional cortex to post-TBI recovery process, however, requires further exploration.