Exploration of Digestive Diseases

Table 1. Biological functions of lysosomal hydrolases during liver fibrosis

Name (Family, MEROPS ID)	Biological process modulated during liver fibrosis
Name (Family, MEROPS ID)	Apoptosis	HSC activation	Autophagy	Inflammation	ECM remodeling
Cathepsin A (Ser, S10.002)	-	-	Degradation of LAMP2a restricting chaperone-mediated autophagy in vitro [48]	-	-
Cathepsin B (Cys, C01.060)	Proteolytic processing of members of the Bcl-2 family in hepatocytes [24]	Modulation of pAkt in HSC after PDGF stimulation contributing to their proliferative and migratory capacity [30]	Cytosolic cathepsin B, released by autophagic flux, triggers activation of NLRP3 in HSC contributing its activation [36]	Participation in the cytotoxic response mediated by TRAIL in NK/NKT cells by an unknown mechanism [39]	Collagenolytic activity by an unknown mechanism [43, 44]
Cathepsin B (Cys, C01.060)		Proteolysis of PDGF receptor-β contributing to PDGF-BB desensitization in HSC [31]		Modulation NF-κB dependent inflammation in HSC via sirtuin-1 regulation [40]	Collagenolytic activity by an unknown mechanism [43, 44]
Cathepsin D (Asp, A01.009)	Proteolytic cleavage of Bid into t-Bid, upstream mitochondria, triggered by TNF-α in hepatocytes [46]	Paracrine activation of cathepsin B in HSC contributing its activation [30]	Correlation of cathepsin D and autophagy during DR in cirrhosis by an unknown mechanism [47]	-	-
Cathepsin F (Cys, C01.018)	-	Transcriptional regulation of markers of HSC activation by an unknown mechanism [35]	-	-	-
Cathepsin H (Cys, C01.040)	-	Modulation of metalloproteinases gene expression in HSC via stabilization of class Iia histone deacetylases [34]	-	-	-
Cathepsin L (Cys, C01.032)	-	-	-	-	Collagenolytic activity by an unknown mechanism [44]
Cathepsin S (Cys, C01.034)	-	-	-	Modulation of NF-κB dependent inflammation in HSC via sirtuin-1 regulation [40]	-
Cathepsin S (Cys, C01.034)	-	-	-	Processing of CD74 contributing to antigen presentation in HSC [41]	-

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pAkt: phosphorylated Akt; -: not applicable

Declarations

Acknowledgments

We would like to sincerely acknowledge all the authors, cited or not, whose work has contributed to the advancement of the research field.

Author contributions

MFF: Writing—original draft. PRB: Writing—original draft. JCP: Writing—original draft. AM: Writing—original draft, Conceptualization, Visualization, Supervision, Funding acquisition, Resources, Project administration, Writing—review & editing.

Conflicts of interest

The authors declare that they have no conflicts of interest.

Ethical approval

Not applicable.

Consent to participate

Not applicable.

Consent to publication

Not applicable.

Availability of data and materials

Not applicable.

Funding

AM’s research is supported by grants [RTI2018-097475-A-100] and [PID2021-123652OB-I00] funded by MCIN/AEI/10.13039/501100011033 and by “ERDF A way of making Europe”, by the “European Union”. Both MFF and PRB salaries were supported by FPU fellowships ([FPU20/01367] and [FPU19/05357], respectively) awarded by the Ministry of Universities, Spain. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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