Fig. 4.

CHI3L1 level was reduced following treatment of GD. (A) Imiglucerase treatment led to reduced level of CHI3L1 in the PGRN KO GD animal model. PGRN KO mice were induced toward a GD phenotype by IP injection of OVA at Day 1 and 15, followed by intranasal challenge of 1% OVA at Day 29 for three times per week for four weeks. One group of mice received imiglucerase (60 μg/kg/week) after Day 29 for four weeks. Lung tissues were collected for immunohistochemistry staining with CHI3L1 specific antibody. (B) PGRN KO mice were induced toward a GD phenotype. Two groups of PGRN KO mice received IP injection of recombinant PGRN protein (4 mg/kg/week) and Pcgin (4 mg/kg/week), respectively, starting after Day 29 for four weeks. Spleen tissues were collected to analyze CHI3L1 expression by western-blot. (C) Quantification of (B) using Image J. (D) Lung tissue sections from PGRN KO mice treated with PGRN or Pcgin from (B) were stained with CHI3L1 specific antibody. (E) Recombinant PGRN injection reduced CHI3L1 expression in Gba1 D409V/null GD mouse model. 5-weeks-old D409V/null mice were injected with PBS or rPGRN (4 mg/kg/week) for 4 weeks and CHI3L1 expression was measured in spleen lysis. (F) Quantification of (E) by Image J. (G–I) CHI3L1 expressions at both mRNA level (G) and protein level (H) were reduced in the fibroblasts of GD patients following treatment with imiglucerase, PGRN, or Pcgin. Fibroblasts were treated with imiglucerase (160 mU/ml), PGRN (1 μg/ml), and Pcgin (1 μg/ml) for 24 and 48 h respectively. The CHI3L1 mRNA levels were measured by quantitative PCR after 24 h and protein levels were examined by western-blot after 48 h treatment. (I) Quantification of (H) by Image J.