Ali Canbay, Maria Eugenia Guicciardi, Hajime Higuchi, Ariel Feldstein, Steven F. Bronk, Robert Rydzewski, Makiko Taniai, Gregory J. Gores
J Clin Invest.
2003;
112(2):152–159
doi:10.1172/JCI17740
This article Copyright © 2003, The American Society for Clinical Investigation
Abstract
|
Full text
|
PDF
A
lthough a lysosomal, cathepsin B–dependent (Ctsb-dependent) pathway of apoptosis has been described, the contribution of this pathway to tissue damage remains unclear. Our aim was to ascertain if Ctsb inactivation attenuates liver injury, inflammation, and fibrogenesis after bile duct ligation (BDL). In 3-day BDL mice, hepatocyte apoptosis, mitochondrial cytochrome c release, and serum alanine aminotransferase (ALT) values were reduced in Ctsb–/– versus Ctsb+/+ animals. Likewise, R-3032 (a Ctsb inhibitor) also reduced these parameters in BDL WT mice. Both genetic and pharmacologic inhibition of Ctsb in the BDL mouse reduced (a) hepatic inflammation, as assessed by transcripts for CXC chemokines and neutrophil infiltration, and (b) fibrogenesis, as assessed by transcripts for stellate cell activation and sirius red staining for hepatic collagen deposition. These differences could not be ascribed to alterations in cholestasis. These findings support a prominent role for the lysosomal pathway of apoptosis in tissue injury and link apoptosis to inflammation and fibrogenesis. Ctsb inhibition may be therapeutic in liver diseases.
This file is in Adobe Acrobat (PDF) format.
If you have not installed and configured the Adobe Acrobat Reader on your system.
Having trouble reading a PDF?
PDFs are designed to be printed out and read, but if you prefer to read them online, you may find it easier if you increase the view size to 125%.
Having trouble saving a PDF?
Many versions of the free Acrobat Reader do not
allow Save. You must instead save the PDF from the JCI Online page you downloaded it from. PC users:
Right-click on the Download link and choose the option that says something like "Save Link As...".
Mac users should hold the mouse button down on the link to get these same options.
Having trouble printing a PDF?
- Try printing one page at a time or to a newer printer.
- Try saving the file to disk before printing rather than opening it "on the fly." This requires that you
configure your browser to "Save" rather than "Launch Application" for the file type "application/pdf", and can
usually be done in the "Helper Applications" options.
- Make sure you are using the latest version of Adobe's Acrobat Reader.
