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Cathepsin L-deficiency enhances liver regeneration after partial hepatectomy
Cathepsin L-deficiency enhances liver regeneration after partial hepatectomy
- Source :
- Life sciences. 221
- Publication Year :
- 2018
-
Abstract
- Aim Cathepsin L (Ctsl) plays a pivotal role in lysosomal and autophagic proteolysis. Previous investigations revealed that partial hepatectomy (PH) decreases biosynthesis of cathepsins in liver, followed by suppression of lysosomal and autophagic proteolysis during liver regeneration. Conversely, it was reported that autophagy-deficiency suppressed liver regeneration. Thus, the purpose of this study is to determine if Ctsl deficiency affects liver regeneration after PH. Methods 70% of PH was performed in male Ctsl-deficient mice (Ctsl−/−) and wild-type littermates (Ctsl +/+) after PH. Mice were sacrificed and wet weight of the whole remaining liver was measured. Bromodeoxyuridine (BrdU)-immunostaining of liver sections was performed. Expression of cyclin D1, p62, LC-3, Nrf2, cleaved-Notch1, Hes1 was evaluated by western blot analysis. NQO1 mRNA expression was measured by realtime-PCR. Results After a 70% of PH, the liver mass was significantly restored within 5 days in Ctsl−/− mice compared to wild-type. Ctsl-deficiency enhanced the increases in both the rate of BrdU-positive cells and cyclin D1 expression after PH more than wild-type mice. On the other hand, Ctsl-deficiency upregulated p62, cleaved-Notch1 and Hes1 expression after PH. Moreover, the protein level of Nrf2 in the nucleus and mRNA expression of NQO1 in the liver after PH was also up-regulated in Ctsl−/− mice. Conclusions These findings suggest that accumulation of p62 due to loss of Ctsl plays an important role in liver regeneration through activation of Nrf2-Notch1 signaling. Taken together, Ctsl might be a new therapeutic target on disorder of liver regeneration.
- Subjects :
- 0301 basic medicine
Male
NF-E2-Related Factor 2
Proteolysis
Cathepsin L
030226 pharmacology & pharmacy
General Biochemistry, Genetics and Molecular Biology
03 medical and health sciences
chemistry.chemical_compound
Mice
0302 clinical medicine
Cyclin D1
Downregulation and upregulation
Western blot
medicine
Autophagy
Animals
Hepatectomy
General Pharmacology, Toxicology and Pharmaceutics
Cells, Cultured
Cathepsin
Mice, Knockout
medicine.diagnostic_test
biology
Receptors, Notch
General Medicine
Molecular biology
Cathepsins
Liver regeneration
Liver Regeneration
030104 developmental biology
chemistry
Liver
biology.protein
Lysosomes
Transcription Factor TFIIH
Bromodeoxyuridine
Signal Transduction
Transcription Factors
Subjects
Details
- ISSN :
- 18790631
- Volume :
- 221
- Database :
- OpenAIRE
- Journal :
- Life sciences
- Accession number :
- edsair.doi.dedup.....4bc26a74fff25fe73980b203831c3f35