Cathepsin B inactivation attenuates hepatic injury and fibrosis during cholestasis
J. Clin. Invest. Ali Canbay, et al. 112:152 doi:10.1172/JCI17740 [
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Figure 4Markers for HSC activation are increased in
Ctsb+/+ compared with
Ctsb–/– and R-3032–treated
Ctsb+/+ BDL mice. Three days after the surgical procedure, liver tissue was procured and total hepatic RNA was isolated as described in Methods. α-SMA, TGF-β1, COL1A1, and TIMP were quantitated by real-time PCR. The expression was normalized as a ratio using 18S and GAPDH mRNA as housekeeping genes. A value of 1 for this ratio was arbitrarily assigned to the data obtained from sham-operated
Ctsb+/+ mice. (
a) α-SMA mRNA expression in
Ctsb+/+ BDL was higher than in
Ctsb–/– (
P < 0.0001) and R-3032–treated
Ctsb+/+ BDL mice (
P < 0.0003,
n = 4 for each group). (
b) The expression of TGF-β1 mRNA was greater in
Ctsb+/+ than in
Ctsb–/– (
P < 0.0001) and R-3032–treated
Ctsb+/+ BDL mice (
P < 0.0001,
n = 4 for each group). (
c) The expression of COL1A1 mRNA was significantly elevated in
Ctsb+/+ BDL mice and markedly attenuated in
Ctsb–/– (
P < 0.0001) and R-3032–treated
Ctsb+/+ BDL mice (
P < 0.0001,
n = 4 for each group). (
d) The expression of TIMP mRNA was not significantly different in
Ctsb+/+,
Ctsb–/–, and R-3032–treated
Ctsb+/+ BDL mice (
P = NS,
n = 4 for each group).