{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T23:50:28Z","timestamp":1792453828210,"version":"4.5.0"},"reference-count":44,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2024,9,1]],"date-time":"2024-09-01T00:00:00Z","timestamp":1725148800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2024,9,1]],"date-time":"2024-09-01T00:00:00Z","timestamp":1725148800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2024,7,8]],"date-time":"2024-07-08T00:00:00Z","timestamp":1720396800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100023561","name":"Government of Spain Ministry of Universities","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100023561","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008648","name":"Pfizer Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008648","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003339","name":"Spanish Scientific Research Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003339","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004837","name":"Ministerio de Ciencia e Innovaci\u00f3n","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004837","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["clinicalkey.fr","clinicalkey.jp","clinicalkey.com.au","clinicalkey.es","clinicalkey.com","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Molecular Metabolism"],"published-print":{"date-parts":[[2024,9]]},"DOI":"10.1016\/j.molmet.2024.101989","type":"journal-article","created":{"date-parts":[[2024,7,15]],"date-time":"2024-07-15T20:06:39Z","timestamp":1721073999000},"page":"101989","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":31,"special_numbering":"C","title":["Cathepsin D is essential for the degradomic shift of macrophages required to resolve liver fibrosis"],"prefix":"10.1016","volume":"87","author":[{"given":"Paloma","family":"Ruiz-Bl\u00e1zquez","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda","family":"Fern\u00e1ndez-Fern\u00e1ndez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valeria","family":"Pistorio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Celia","family":"Martinez-Sanchez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michele","family":"Costanzo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paula","family":"Iruzubieta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ekaterina","family":"Zhuravleva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00falia","family":"Cacho-Pujol","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Ari\u00f1o","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alejandro","family":"Del Castillo-Cruz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susana","family":"N\u00fa\u00f1ez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jesper B.","family":"Andersen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margherita","family":"Ruoppolo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Javier","family":"Crespo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmen","family":"Garc\u00eda-Ruiz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luigi Michele","family":"Pavone","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Reinheckel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pau","family":"Sancho-Bru","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar","family":"Coll","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 C.","family":"Fern\u00e1ndez-Checa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3915-0060","authenticated-orcid":false,"given":"Anna","family":"Moles","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.molmet.2024.101989_bib1","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1038\/nri1412","article-title":"Fibrotic disease and the T(H)1\/T(H)2 paradigm","volume":"4","author":"Wynn","year":"2004","journal-title":"Nat Rev Immunol"},{"key":"10.1016\/j.molmet.2024.101989_bib2","doi-asserted-by":"crossref","first-page":"1557","DOI":"10.1002\/hep.29085","article-title":"Increased risk of mortality by fibrosis stage in nonalcoholic fatty liver disease: systematic review and meta-analysis","volume":"65","author":"Dulai","year":"2017","journal-title":"Hepatology"},{"key":"10.1016\/j.molmet.2024.101989_bib3","doi-asserted-by":"crossref","first-page":"1192","DOI":"10.1016\/j.jhep.2021.06.031","article-title":"The multifaceted role of cathepsins in liver disease","volume":"75","author":"Ruiz-Bl\u00e1zquez","year":"2021","journal-title":"J\u00a0Hepatol"},{"key":"10.1016\/j.molmet.2024.101989_bib4","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1172\/JCI200317740","article-title":"Cathepsin B inactivation attenuates hepatic injury and fibrosis during cholestasis","volume":"112","author":"Canbay","year":"2003","journal-title":"J\u00a0Clin Invest"},{"key":"10.1016\/j.molmet.2024.101989_bib5","doi-asserted-by":"crossref","first-page":"1297","DOI":"10.1002\/hep.22753","article-title":"Cathepsins B and D drive hepatic stellate cell proliferation and promote their fibrogenic potential","volume":"49","author":"Moles","year":"2009","journal-title":"Hepatology"},{"key":"10.1016\/j.molmet.2024.101989_bib6","doi-asserted-by":"crossref","first-page":"1178","DOI":"10.1074\/jbc.M111.272393","article-title":"Cathepsin B overexpression due to acid sphingomyelinase ablation promotes liver fibrosis in Niemann-Pick disease","volume":"287","author":"Moles","year":"2012","journal-title":"J\u00a0Biol Chem"},{"key":"10.1016\/j.molmet.2024.101989_bib7","doi-asserted-by":"crossref","first-page":"1214","DOI":"10.2353\/ajpath.2010.091257","article-title":"Acidic sphingomyelinase controls hepatic stellate cell activation and in\u00a0vivo liver fibrogenesis","volume":"177","author":"Moles","year":"2010","journal-title":"Am J Pathol"},{"key":"10.1016\/j.molmet.2024.101989_bib8","doi-asserted-by":"crossref","first-page":"3599","DOI":"10.1002\/j.1460-2075.1995.tb00029.x","article-title":"Mice deficient for the lysosomal proteinase cathepsin D exhibit progressive atrophy of the intestinal mucosa and profound destruction of lymphoid cells","volume":"14","author":"Saftig","year":"1995","journal-title":"EMBO J"},{"key":"10.1016\/j.molmet.2024.101989_bib9","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1016\/j.biochi.2015.07.020","article-title":"Neuroectoderm-specific deletion of cathepsin D in mice models human inherited neuronal ceroid lipofuscinosis type 10","volume":"122","author":"Ketscher","year":"2016","journal-title":"Biochimie"},{"key":"10.1016\/j.molmet.2024.101989_bib10","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1023\/A:1008942828960","article-title":"Conditional gene targeting in macrophages and granulocytes using LysMcre mice","volume":"8","author":"Clausen","year":"1999","journal-title":"Transgenic Res"},{"key":"10.1016\/j.molmet.2024.101989_bib11","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1074\/jbc.274.1.305","article-title":"Dual roles for glucokinase in glucose homeostasis as determined by liver and pancreatic \u03b2 cell-specific gene knock-outs using cre recombinase","volume":"274","author":"Postic","year":"1999","journal-title":"J\u00a0Biol Chem"},{"key":"10.1016\/j.molmet.2024.101989_bib12","first-page":"693","article-title":"Characterization of the proximal estrogen-responsive element of human cathepsin D gene","volume":"8","author":"Augereau","year":"1994","journal-title":"Mol Endocrinol"},{"key":"10.1016\/j.molmet.2024.101989_bib13","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1073\/pnas.90.1.203","article-title":"Cathepsin D gene is controlled by a mixed promoter, and estrogens stimulate only TATA-dependent transcription in breast cancer cells","volume":"90","author":"Cavaill\u00e8s","year":"1993","journal-title":"Proc Natl Acad Sci USA"},{"key":"10.1016\/j.molmet.2024.101989_bib14","doi-asserted-by":"crossref","first-page":"512","DOI":"10.1038\/s41586-019-1631-3","article-title":"Resolving the fibrotic niche of human liver cirrhosis at single-cell level","volume":"575","author":"Ramachandran","year":"2019","journal-title":"Nature"},{"key":"10.1016\/j.molmet.2024.101989_bib15","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1007\/BF00708198","article-title":"Localization of cathepsin D in rat liver","volume":"82","author":"Yokota","year":"1985","journal-title":"Histochemistry"},{"key":"10.1016\/j.molmet.2024.101989_bib16","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1002\/hep.31644","article-title":"Programmed death ligand 1 is overexpressed in liver macrophages in chronic liver diseases, and its blockade improves the antibacterial activity against infections","volume":"74","author":"Pose","year":"2021","journal-title":"Hepatology"},{"key":"10.1016\/j.molmet.2024.101989_bib17","doi-asserted-by":"crossref","first-page":"655","DOI":"10.1016\/j.immuni.2019.09.002","article-title":"Liver-derived signals sequentially reprogram myeloid enhancers to initiate and maintain kupffer cell identity","volume":"51","author":"Sakai","year":"2019","journal-title":"Immunity"},{"key":"10.1016\/j.molmet.2024.101989_bib18","doi-asserted-by":"crossref","first-page":"758","DOI":"10.1016\/j.jhep.2016.05.037","article-title":"Bone marrow-derived and resident liver macrophages display unique transcriptomic signatures but similar biological functions","volume":"65","author":"Beattie","year":"2016","journal-title":"J\u00a0Hepatol"},{"key":"10.1016\/j.molmet.2024.101989_bib19","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1111\/j.1432-1033.1981.tb06172.x","article-title":"Cathepsin D: specificity of peptide-bond cleavage in type-I collagen and effects on type-III collagen and procollagen","volume":"114","author":"Scott","year":"2005","journal-title":"Eur J Biochem"},{"key":"10.1016\/j.molmet.2024.101989_bib20","doi-asserted-by":"crossref","first-page":"771","DOI":"10.1681\/ASN.2006091056","article-title":"Presentation of the goodpasture autoantigen requires proteolytic unlocking steps that destroy prominent T cell epitopes","volume":"18","author":"Zou","year":"2007","journal-title":"J\u00a0Am Soc Nephrol"},{"key":"10.1016\/j.molmet.2024.101989_bib21","doi-asserted-by":"crossref","first-page":"2420","DOI":"10.1002\/art.23654","article-title":"Characterization of metalloprotease cleavage products of human articular cartilage","volume":"58","author":"Zhen","year":"2008","journal-title":"Arthritis Rheum"},{"key":"10.1016\/j.molmet.2024.101989_bib22","doi-asserted-by":"crossref","first-page":"894","DOI":"10.1074\/mcp.M000050-MCP201","article-title":"Multiplex N-terminome analysis of MMP-2 and MMP-9 substrate degradomes by iTRAQ-TAILS quantitative proteomics","volume":"9","author":"Prudova","year":"2010","journal-title":"Mol Cell Proteomics"},{"key":"10.1016\/j.molmet.2024.101989_bib23","doi-asserted-by":"crossref","first-page":"2193","DOI":"10.1074\/jbc.M105485200","article-title":"Processing of type II procollagen amino propeptide by matrix metalloproteinases","volume":"277","author":"Fukui","year":"2002","journal-title":"J\u00a0Biol Chem"},{"key":"10.1016\/j.molmet.2024.101989_bib24","doi-asserted-by":"crossref","first-page":"2455","DOI":"10.15252\/embj.201796750","article-title":"Protease cleavage site fingerprinting by label-free in-gel degradomics reveals <scp>pH<\/scp> -dependent specificity switch of legumain","volume":"36","author":"Vidmar","year":"2017","journal-title":"EMBO J"},{"key":"10.1016\/j.molmet.2024.101989_bib25","doi-asserted-by":"crossref","DOI":"10.1053\/j.gastro.2023.05.039","article-title":"Macrophage-derived cathepsin S remodels the extracellular matrix to promote liver fibrogenesis","author":"Zuo","year":"2023","journal-title":"Gastroenterology"},{"key":"10.1016\/j.molmet.2024.101989_bib26","doi-asserted-by":"crossref","first-page":"818","DOI":"10.1074\/mcp.RA118.001304","article-title":"Integration of two in-depth quantitative proteomics approaches determines the kallikrein-related peptidase 7 (KLK7) degradome in ovarian cancer cell secretome","volume":"18","author":"Silva","year":"2019","journal-title":"Mol Cell Proteomics"},{"key":"10.1016\/j.molmet.2024.101989_bib27","doi-asserted-by":"crossref","first-page":"6173","DOI":"10.7150\/thno.58254","article-title":"A\u00a09-kDa matricellular SPARC fragment released by cathepsin D exhibits pro-tumor activity in the triple-negative breast cancer microenvironment","volume":"11","author":"Alcaraz","year":"2021","journal-title":"Theranostics"},{"key":"10.1016\/j.molmet.2024.101989_bib28","doi-asserted-by":"crossref","DOI":"10.1073\/pnas.1119964109","article-title":"Differential Ly-6C expression identifies the recruited macrophage phenotype, which orchestrates the regression of murine liver fibrosis","volume":"109","author":"Ramachandran","year":"2012","journal-title":"Proc Natl Acad Sci USA"},{"key":"10.1016\/j.molmet.2024.101989_bib29","doi-asserted-by":"crossref","first-page":"1373","DOI":"10.1016\/j.jhep.2022.06.004","article-title":"Soluble TREM2 levels reflect the recruitment and expansion of TREM2+ macrophages that localize to fibrotic areas and limit NASH","volume":"77","author":"Hendrikx","year":"2022","journal-title":"J\u00a0Hepatol"},{"key":"10.1016\/j.molmet.2024.101989_bib30","doi-asserted-by":"crossref","first-page":"1266","DOI":"10.1096\/fj.05-5517fje","article-title":"Lysosomal, cytoskeletal, and metabolic alterations in cardiomyopathy of cathepsin L knockout mice","volume":"20","author":"Petermann","year":"2006","journal-title":"Faseb J"},{"key":"10.1016\/j.molmet.2024.101989_bib31","doi-asserted-by":"crossref","first-page":"2203","DOI":"10.1016\/S0002-9440(10)63777-7","article-title":"Pivotal role of cathepsin K in lung fibrosis","volume":"164","author":"B\u00fchling","year":"2004","journal-title":"Am J Pathol"},{"key":"10.1016\/j.molmet.2024.101989_bib32","doi-asserted-by":"crossref","first-page":"647","DOI":"10.1016\/0016-5085(81)90120-7","article-title":"Proteolytic enzymes released by liver macrophages may promote hepatic injury in a rat model of hepatic damage","volume":"80","author":"Tanner","year":"1981","journal-title":"Gastroenterology"},{"key":"10.1016\/j.molmet.2024.101989_bib33","doi-asserted-by":"crossref","first-page":"2805","DOI":"10.1002\/eji.201141538","article-title":"Extracellular proteolysis in macrophage migration: losing grip for a breakthrough","volume":"41","author":"V\u00e9rollet","year":"2011","journal-title":"Eur J Immunol"},{"key":"10.1016\/j.molmet.2024.101989_bib34","article-title":"The roles of neutrophils in the pathogenesis of liver diseases","volume":"12","author":"Tang","year":"2021","journal-title":"Front Immunol"},{"key":"10.1016\/j.molmet.2024.101989_bib35","doi-asserted-by":"crossref","first-page":"782","DOI":"10.1016\/j.jhep.2013.12.005","article-title":"A\u00a0TLR2\/S100A9\/CXCL-2 signaling network is necessary for neutrophil recruitment in acute and chronic liver injury in the mouse","volume":"60","author":"Moles","year":"2014","journal-title":"J\u00a0Hepatol"},{"key":"10.1016\/j.molmet.2024.101989_bib36","doi-asserted-by":"crossref","first-page":"L709","DOI":"10.1152\/ajplung.00418.2012","article-title":"Always cleave up your mess: targeting collagen degradation to treat tissue fibrosis","volume":"304","author":"McKleroy","year":"2013","journal-title":"Am. J. Physiol. Cell. Mol. Physiol."},{"key":"10.1016\/j.molmet.2024.101989_bib37","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0082415","article-title":"Cathepsin E deficiency impairs autophagic proteolysis in macrophages","volume":"8","author":"Tsukuba","year":"2013","journal-title":"PLoS One"},{"key":"10.1016\/j.molmet.2024.101989_bib38","doi-asserted-by":"crossref","first-page":"951","DOI":"10.1083\/jcb.201301081","article-title":"M2-like macrophages are responsible for collagen degradation through a mannose receptor\u2013mediated pathway","volume":"202","author":"Madsen","year":"2013","journal-title":"J\u00a0Cell Biol"},{"key":"10.1016\/j.molmet.2024.101989_bib39","doi-asserted-by":"crossref","DOI":"10.4161\/onci.27127","article-title":"Imaging collagen degradation in\u00a0vivo highlights a key role for M2-polarized macrophages in extracellular matrix degradation","volume":"2","author":"Madsen","year":"2013","journal-title":"OncoImmunology"},{"key":"10.1016\/j.molmet.2024.101989_bib40","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1016\/j.immuni.2020.08.004","article-title":"Osteopontin expression identifies a subset of recruited macrophages distinct from kupffer cells in the fatty liver","volume":"53","author":"Remmerie","year":"2020","journal-title":"Immunity"},{"key":"10.1016\/j.molmet.2024.101989_bib41","doi-asserted-by":"crossref","first-page":"2579","DOI":"10.3390\/cancers12092579","article-title":"Cathepsin inhibition modulates metabolism and polarization of tumor-associated macrophages","volume":"12","author":"Oelschlaegel","year":"2020","journal-title":"Cancers"},{"key":"10.1016\/j.molmet.2024.101989_bib42","doi-asserted-by":"crossref","DOI":"10.1242\/dmm.014050","article-title":"Loss of lysosomal protein NCU-G1 results in spontaneous liver fibrosis with accumulation of lipofuscin and iron in Kupffer cells","author":"Kong","year":"2014","journal-title":"Dis. Model. Mech"},{"key":"10.1016\/j.molmet.2024.101989_bib43","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1186\/s13069-016-0042-4","article-title":"Age-dependent development of liver fibrosis in Glmp gt\/gt mice","volume":"9","author":"Nesset","year":"2016","journal-title":"Fibrogenesis Tissue Repair"},{"key":"10.1016\/j.molmet.2024.101989_bib44","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0054962","article-title":"Lack of the matricellular protein SPARC (secreted protein, acidic and rich in cysteine) attenuates liver fibrogenesis in mice","volume":"8","author":"Atorrasagasti","year":"2013","journal-title":"PLoS One"}],"container-title":["Molecular Metabolism"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2212877824001200?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2212877824001200?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2024,10,9]],"date-time":"2024-10-09T22:11:57Z","timestamp":1728511917000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S2212877824001200"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,9]]},"references-count":44,"alternative-id":["S2212877824001200"],"URL":"https:\/\/doi.org\/10.1016\/j.molmet.2024.101989","relation":{},"ISSN":["2212-8778"],"issn-type":[{"value":"2212-8778","type":"print"}],"subject":[],"published":{"date-parts":[[2024,9]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Cathepsin D is essential for the degradomic shift of macrophages required to resolve liver fibrosis","name":"articletitle","label":"Article Title"},{"value":"Molecular Metabolism","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.molmet.2024.101989","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2024 The Authors. Published by Elsevier GmbH.","name":"copyright","label":"Copyright"}],"article-number":"101989"}}