{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T13:19:16Z","timestamp":1785417556250,"version":"3.56.0"},"reference-count":94,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T00:00:00Z","timestamp":1784678400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"The First Hospital of Lanzhou University","award":["ldyyyn2020-51"],"award-info":[{"award-number":["ldyyyn2020-51"]}]},{"award":["ldyyyn2020-51"],"award-info":[{"award-number":["ldyyyn2020-51"]}],"id":[{"id":"https:\/\/ror.org\/05d2xpa49","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>Myocardial ischemia and reperfusion initiate spatially organized injury\u2013repair programs that subsequently shape ventricular remodeling. Although cardiac fibroblasts are indispensable for scar formation, single-cell and spatial transcriptomic studies reveal temporally dynamic and regionally distinct fibroblast-lineage states. This critical narrative review integrates direct evidence from myocardial ischemia\u2013reperfusion (I\/R) with model-labeled evidence from permanent myocardial infarction, clinically heterogeneous human infarction, fibroblast-specific ubiquitin biology, cell-cycle regulation, and cardiac fibroblast atlases. A direct fibroblast I\/R study identifies an HSP47\u2013USP10\u2013SMAD4 deubiquitination axis, whereas most other fibroblast ubiquitin\u2013proteasome system (UPS) mechanisms derive from permanent infarction, non-ischemic cardiac stress, or in vitro systems. We propose that CCNB1-associated, G2\/M-enriched cycling fibroblast-lineage states may impose heightened proteostatic demands within defined post-ischemic niches. The conceptual novelty is not that CCNB1 turnover or UPS activity is cardiac-specific; both are general features of proliferating cells. Rather, the framework asks whether fibroblast lineage, injury-model provenance, anatomical niche, temporal window, cell state, and substrate-specific UPS nodes jointly define proteostatic dependencies during post-ischemic remodeling. RNA-based ubiquitin-related signatures remain transcriptional proxies and do not directly quantify ubiquitinated substrates, ubiquitin-chain topology, enzyme activity, or proteasome flux. Resolving the proposed relationships will require spatial colocalization, protein-level and ubiquitin-remnant profiling, proteasome and ribosome assays, fibroblast-specific perturbation, and validation in human infarct tissue.<\/jats:p>","DOI":"10.3390\/ijms27146537","type":"journal-article","created":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T01:01:28Z","timestamp":1784768488000},"page":"6537","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Ubiquitin-Related Proteostatic Programs in Cycling Fibroblast-Lineage Remodeling After Myocardial Ischemic Injury: A Hypothesis Informed by Single-Cell and Spatial Transcriptomics"],"prefix":"10.3390","volume":"27","author":[{"given":"Chengcheng","family":"Yi","sequence":"first","affiliation":[{"name":"The First Clinical Medical College, Lanzhou University, Lanzhou 730000, China"},{"name":"Heart Center, The First Hospital of Lanzhou University, Lanzhou 730000, China"},{"name":"Key Laboratory for Cardiovascular Diseases of Gansu Province, The First Hospital of Lanzhou University, Lanzhou 730000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenyuan","family":"Zheng","sequence":"additional","affiliation":[{"name":"Heart Center, The First Hospital of Lanzhou University, Lanzhou 730000, China"},{"name":"Key Laboratory for Cardiovascular Diseases of Gansu Province, The First Hospital of Lanzhou University, Lanzhou 730000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Zhao","sequence":"additional","affiliation":[{"name":"The First Clinical Medical College, Lanzhou University, Lanzhou 730000, China"},{"name":"Heart Center, The First Hospital of Lanzhou University, Lanzhou 730000, China"},{"name":"Key Laboratory for Cardiovascular Diseases of Gansu Province, The First Hospital of Lanzhou University, Lanzhou 730000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiting","family":"Cai","sequence":"additional","affiliation":[{"name":"The First Clinical Medical College, Lanzhou University, Lanzhou 730000, China"},{"name":"Heart Center, The First Hospital of Lanzhou University, Lanzhou 730000, China"},{"name":"Key Laboratory for Cardiovascular Diseases of Gansu Province, The First Hospital of Lanzhou University, Lanzhou 730000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junqian","family":"Wang","sequence":"additional","affiliation":[{"name":"Heart Center, The First Hospital of Lanzhou University, Lanzhou 730000, China"},{"name":"Key Laboratory for Cardiovascular Diseases of Gansu Province, The First Hospital of Lanzhou University, Lanzhou 730000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Song","sequence":"additional","affiliation":[{"name":"Heart Center, The First Hospital of Lanzhou University, Lanzhou 730000, China"},{"name":"Key Laboratory for Cardiovascular Diseases of Gansu Province, The First Hospital of Lanzhou University, Lanzhou 730000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming","family":"Bai","sequence":"additional","affiliation":[{"name":"The First Clinical Medical College, Lanzhou University, Lanzhou 730000, China"},{"name":"Heart Center, The First Hospital of Lanzhou University, Lanzhou 730000, China"},{"name":"Key Laboratory for Cardiovascular Diseases of Gansu Province, The First Hospital of Lanzhou University, Lanzhou 730000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zheng","family":"Zhang","sequence":"additional","affiliation":[{"name":"The First Clinical Medical College, Lanzhou University, Lanzhou 730000, China"},{"name":"Heart Center, The First Hospital of Lanzhou University, Lanzhou 730000, China"},{"name":"Key Laboratory for Cardiovascular Diseases of Gansu Province, The First Hospital of Lanzhou University, Lanzhou 730000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1172\/JCI62874","article-title":"Myocardial ischemia-reperfusion injury: A neglected therapeutic target","volume":"123","author":"Hausenloy","year":"2013","journal-title":"J. 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