The DOI matches its Crossref record; 2 of the 2 references it cites were found in a registry or an index.
Cathepsin B inactivation attenuates hepatic injury and fibrosis during cholestasis
Open accessAbstract
Although 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.
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Cites
Murphy, F. R., Issa, R., Zhou, X., Ratnarajah, S., Arthur, M. J. P., Benyon, C., Iredale, J. P., & Nagase, H. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m111490200 · Cited by 432
Apoptotic Body Engulfment by a Human Stellate Cell Line Is Profibrogenic
Canbay, A., Taimr, P., Torok, N., Higuchi, H., Friedman, S., & Gores, G. J. (2003) · Laboratory Investigation · doi:10.1097/01.lab.0000069036.63405.5c · Cited by 417
Self-citation
Cited by
Bataller, R., & Brenner, D. A. (2005) · Journal of Clinical Investigation · doi:10.1172/jci24282 · Cited by 4,958
Lysosomal membrane permeabilization in cell death
Boya, P., & Kroemer, G. (2008) · Oncogene · doi:10.1038/onc.2008.310 · Cited by 1,426
Caspase-independent cell death
Kroemer, G., & Martin, S. J. (2005) · Nature Medicine · doi:10.1038/nm1263 · Cited by 716
Lysosomal cell death at a glance
Aits, S., & Jäättelä, M. (2013) · Journal of Cell Science · doi:10.1242/jcs.091181 · Cited by 667
Increased stiffness of the rat liver precedes matrix deposition: implications for fibrosis
Georges, P. C., Hui, J.-J., Gombos, Z., McCormick, M. E., Wang, A. Y., Uemura, M., Mick, R., Janmey, P. A., Furth, E. E., & Wells, R. G. (2007) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00032.2007 · Cited by 577
Metadata
- Authors
- Canbay, A., Guicciardi, M. E., Higuchi, H., Feldstein, A., Bronk, S. F., Rydzewski, R., Taniai, M., & Gores, G. J.
- Venue
- Journal of Clinical Investigation
- Published
- 2003-07-15
- Volume
- 112
- Issue
- 2
- Pages
- 152-159
- ISSN
- 0021-9738 (ISSN-L)
- OpenAlex
- W4244029562
- Cited by
- 188
- References
- 2
- FWCI
- 11.01
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Canbay, A., Guicciardi, M. E., Higuchi, H., Feldstein, A., Bronk, S. F., Rydzewski, R., Taniai, M., & Gores, G. J. (2003). Cathepsin B inactivation attenuates hepatic injury and fibrosis during cholestasis. Journal of Clinical Investigation. https://doi.org/10.1172/jci200317740
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