{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T09:08:37Z","timestamp":1788858517336,"version":"build-2803163510"},"reference-count":97,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T00:00:00Z","timestamp":1788825600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Collagen is the most abundant protein in the human body and a vital component of the extracellular matrix (ECM), where it maintains structural architecture, strength, and mechanical stability throughout the body. Collagen undergoes continuous turnover and remodeling mediated by matrix metalloproteinases (MMPs) and other proteases to generate collagen peptide fragments (CPFs). CPFs were long considered inert byproducts of collagen turnover but are now recognized to have two overlapping roles: as circulating and urinary biomarkers of ECM remodeling, and as beneficial or adverse bioactive matrikines that directly regulate inflammation, angiogenesis, fibrosis, immune responses, and tissue remodeling. This review focuses on current evidence regarding the biological activities of various CPFs across cardiovascular, cancer, and pulmonary systems. We conclude by discussing various perspectives, including clinical and therapeutic applications and future directions.<\/jats:p>","DOI":"10.3390\/cells15181626","type":"journal-article","created":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T08:10:22Z","timestamp":1788855022000},"page":"1626","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Current Perspectives on the Role of Collagen Peptide Fragments in Health and Disease"],"prefix":"10.3390","volume":"15","author":[{"given":"Kenzi-Alayna","family":"Campbell","sequence":"first","affiliation":[{"name":"Department of Physiology, Brody School of Medicine at East Carolina University, Greenville, NC 27834, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanjay P.","family":"Tirupattur","sequence":"additional","affiliation":[{"name":"Department of Physiology, Brody School of Medicine at East Carolina University, Greenville, NC 27834, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gia","family":"Katwa","sequence":"additional","affiliation":[{"name":"Department of Physiology, Brody School of Medicine at East Carolina University, Greenville, NC 27834, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7479-4630","authenticated-orcid":false,"given":"Laxmansa C.","family":"Katwa","sequence":"additional","affiliation":[{"name":"Department of Physiology, Brody School of Medicine at East Carolina University, Greenville, NC 27834, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"4064","DOI":"10.1111\/febs.70444","article-title":"An Update on the Landscape of Collagen Bioactive Fragments","volume":"293","author":"Fradette","year":"2026","journal-title":"FEBS J."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"5","DOI":"10.26502\/fccm.92920302","article-title":"Regulation of Collagen I and Collagen III in Tissue Injury and Regeneration","volume":"7","author":"Singh","year":"2023","journal-title":"Cardiol. Cardiovasc. Med."},{"key":"ref_3","first-page":"a004978","article-title":"The Collagen Family","volume":"3","year":"2010","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1016\/j.lfs.2019.04.042","article-title":"What Is the Role of Peptide Fragments of Collagen I and IV in Health and Disease?","volume":"228","author":"Kisling","year":"2019","journal-title":"Life Sci."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1210\/endrev\/bnad036","article-title":"Endotrophin, a Key Marker and Driver for Fibroinflammatory Disease","volume":"45","author":"Henriksen","year":"2024","journal-title":"Endocr. Rev."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"100139","DOI":"10.1016\/j.mbplus.2023.100139","article-title":"Designing Collagens to Shed Light on the Multi-Scale Structure\u2013Function Mapping of Matrix Disorders","volume":"21","author":"Gahlawat","year":"2024","journal-title":"Matrix Biol. Plus"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1007\/s00441-009-0844-4","article-title":"Collagens","volume":"339","author":"Gordon","year":"2010","journal-title":"Cell Tissue Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"e24176","DOI":"10.7554\/eLife.24176","article-title":"Collagen IV and Basement Membrane at the Evolutionary Dawn of Metazoan Tissues","volume":"6","author":"Fidler","year":"2017","journal-title":"eLife"},{"key":"ref_9","first-page":"191","article-title":"Biological Role of Matrix Metalloproteinases: A Critical Balance","volume":"38","author":"Schilling","year":"2010","journal-title":"Eur. Respir. J."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1111\/joim.12819","article-title":"A Biomarker of Collagen Type I Degradation Is Associated with Cardiovascular Events and Mortality in Patients with Atherosclerosis","volume":"285","author":"Tengryd","year":"2019","journal-title":"J. Intern. Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"020502","DOI":"10.11613\/BM.2026.020502","article-title":"Procollagen I Carboxy-Terminal Propeptide: A Multi-Faceted Biomarker","volume":"36","author":"Jain","year":"2026","journal-title":"Biochem. Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1331","DOI":"10.1093\/aje\/kwu067","article-title":"Fibrosis-Related Biomarkers and Risk of Total and Cause-Specific Mortality","volume":"179","author":"Agarwal","year":"2014","journal-title":"Am. J. Epidemiol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"e2000027","DOI":"10.1002\/prca.202000027","article-title":"Value of Urine Peptides in Assessing Kidney and Cardiovascular Disease","volume":"15","author":"Latosinska","year":"2021","journal-title":"Proteom. Clin. Appl."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"121598","DOI":"10.1016\/j.lfs.2023.121598","article-title":"Collagen Matricryptin Promotes Cardiac Function by Mediating Scar Formation","volume":"312","author":"Grilo","year":"2023","journal-title":"Life Sci."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Zhou, Y., Jiang, Z., Cao, L., and Yang, J. (2025). The Role of Various Collagen Types in Tumor Biology: A Review. Front. Oncol., 15.","DOI":"10.3389\/fonc.2025.1549797"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"152346","DOI":"10.1016\/j.seminoncol.2025.152346","article-title":"The Crucial Nexus: Unveiling the Role of Collagen in Cancer Progression","volume":"52","author":"Reeva","year":"2025","journal-title":"Semin. Oncol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1186\/s40733-022-00084-6","article-title":"A Serological Biomarker of Type I Collagen Degradation Is Related to a More Severe, High Neutrophilic, Obese Asthma Subtype","volume":"8","author":"Sand","year":"2022","journal-title":"Asthma Res. Pract."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1186\/s12931-019-1026-x","article-title":"Type IV Collagen Turnover Is Predictive of Mortality in COPD: A Comparison to Fibrinogen in a Prospective Analysis of the ECLIPSE Cohort","volume":"20","author":"Sand","year":"2019","journal-title":"Respir. Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1038\/nm1361","article-title":"A Novel Peptide CXCR Ligand Derived from Extracellular Matrix Degradation during Airway Inflammation","volume":"12","author":"Weathington","year":"2006","journal-title":"Nat. Med."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"e70089","DOI":"10.1002\/clt2.70089","article-title":"Genetic and Environmental Contributions to Serological Biomarkers of Extracellular Matrix Remodeling in Asthma: A Twin Study","volume":"15","author":"Andelic","year":"2025","journal-title":"Clin. Transl. Allergy"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"11","DOI":"10.5334\/gh.1288","article-title":"The Heart of the World","volume":"19","author":"McGhie","year":"2024","journal-title":"Glob. Heart"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"733","DOI":"10.1161\/CIRCHEARTFAILURE.111.962027","article-title":"The Relationship between Serum Markers of Collagen Turnover and Cardiovascular Outcome in the Elderly: The Cardiovascular Health Study","volume":"4","author":"Barasch","year":"2011","journal-title":"Circ. Heart Fail."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2727","DOI":"10.1161\/CIRCULATIONAHA.110.942268","article-title":"Molecular Pathways Underlying Cardiac Remodeling during Pathophysiological Stimulation","volume":"122","author":"Kehat","year":"2010","journal-title":"Circulation"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"\u015awi\u0105tko, M., Baran, J.M., Czernicka, A., Dudek, \u0141., Szewczyk, M., Pietruszka, J., \u0141azarowicz, \u0141., Kochman, W., and Dziedzic, E.A. (2026). Myocardial Fibrosis in Cardiovascular Disease: An Integrative Biomarker\u2013Imaging Framework Linking Molecular Mechanisms to Structural Phenotypes. J. Clin. Med., 15.","DOI":"10.3390\/jcm15103742"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1216","DOI":"10.1253\/circj.CJ-25-0067","article-title":"Effect of Serum Carboxyl-Terminal Telopeptide of Type I Collagen on Clinical Outcomes in Patients with Coronary Artery Disease","volume":"89","author":"Otaki","year":"2025","journal-title":"Circ. J."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2042","DOI":"10.1016\/j.amjcard.2017.03.036","article-title":"Usefulness of Collagen Carboxy-Terminal Propeptide and Telopeptide to Predict Disturbances of Long-Term Mortality in Patients \u2265 60 Years with Heart Failure and Reduced Ejection Fraction","volume":"119","author":"Kahan","year":"2017","journal-title":"Am. J. Cardiol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"5371","DOI":"10.1038\/s41598-018-23458-4","article-title":"Matrix Metalloproteinase Mediated Type I Collagen Degradation Is an Independent Predictor of Increased Risk of Acute Myocardial Infarction in Postmenopausal Women","volume":"8","author":"Bertelsen","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"e202400279","DOI":"10.1002\/pmic.202400279","article-title":"Investigation of the Urinary Peptidome to Unravel Collagen Degradation in Health and Kidney Disease","volume":"25","author":"Mina","year":"2025","journal-title":"Proteomics"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"e267","DOI":"10.1002\/ctm2.267","article-title":"Serum and Urinary Biomarkers of Collagen Type-I Turnover Predict Prognosis in Patients with Heart Failure","volume":"11","author":"He","year":"2021","journal-title":"Clin. Transl. Med."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1331","DOI":"10.1097\/HJH.0000000000003726","article-title":"Multiple Urinary Peptides Are Associated with Hypertension: A Link to Molecular Pathophysiology","volume":"42","author":"Mavrogeorgis","year":"2024","journal-title":"J. Hypertens."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1489","DOI":"10.1016\/S0002-9440(10)65020-1","article-title":"Regulation of Tissue Injury Responses by Matricryptic Sites","volume":"156","author":"Davis","year":"2000","journal-title":"Am. J. Pathol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1364","DOI":"10.1016\/j.jacc.2015.07.035","article-title":"A Novel Collagen Matricryptin Reduces Left Ventricular Dilation Post-Myocardial Infarction by Promoting Scar Formation and Angiogenesis","volume":"66","author":"Lindsey","year":"2015","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_33","first-page":"10","article-title":"Cancer Statistics, 2025","volume":"75","author":"Siegel","year":"2025","journal-title":"CA Cancer J. Clin."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Necula, L., Matei, L., Dragu, D., Pitica, I., Neagu, A., Bleotu, C., Diaconu, C.C., and Chivu-Economescu, M. (2022). Collagen Family as Promising Biomarkers and Therapeutic Targets in Cancer. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms232012415"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1002\/path.6207","article-title":"The Collagen Landscape in Cancer: Profiling Collagens in Tumors and in Circulation Reveals Novel Markers of Cancer-Associated Fibroblast Subtypes","volume":"262","author":"Jensen","year":"2024","journal-title":"J. Pathol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"108330","DOI":"10.1016\/j.jbc.2025.108330","article-title":"Collagen Remodeling-Mediated Signaling Pathways and Their Impact on Tumor Therapy","volume":"301","author":"Yuan","year":"2025","journal-title":"J. Biol. Chem."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"117423","DOI":"10.1016\/j.biopha.2024.117423","article-title":"Recombinant Canstatin Inhibits the Progression of Hepatocellular Carcinoma by Repressing the HIF-1\u03b1\/VEGF Signaling Pathway","volume":"179","author":"Zhu","year":"2024","journal-title":"Biomed. Pharmacother."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1117","DOI":"10.1177\/1947601911423654","article-title":"Hypoxia-Induced Angiogenesis","volume":"2","author":"Krock","year":"2011","journal-title":"Genes Cancer"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1016\/S0092-8674(00)81848-6","article-title":"Endostatin: An Endogenous Inhibitor of Angiogenesis and Tumor Growth","volume":"88","author":"Boehm","year":"1997","journal-title":"Cell"},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Sun, J., Ren, S., Zhao, Q., He, J., Wang, Y., and Ren, M. (2025). Endostatin-Based Anti-Angiogenic Therapy and Immune Modulation: Mechanisms and Synergistic Potential in Cancer Treatment. Front. Immunol., 16.","DOI":"10.3389\/fimmu.2025.1623859"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1406","DOI":"10.1007\/s12094-024-03667-2","article-title":"Emerging Immunologic Approaches as Cancer Anti-Angiogenic Therapies","volume":"27","author":"Azimi","year":"2025","journal-title":"Clin. Transl. Oncol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"2589","DOI":"10.1016\/j.bbagen.2013.12.029","article-title":"Matrikines from Basement Membrane Collagens: A New Anti-Cancer Strategy","volume":"1840","author":"Monboisse","year":"2014","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_43","first-page":"1874","article-title":"Endostatin Reverses Immunosuppression of the Tumor Microenvironment in Lung Carcinoma","volume":"15","author":"Liu","year":"2018","journal-title":"Oncol. Lett."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1007\/s10989-022-10458-2","article-title":"Novel Anti-Angiogenic Peptide Derived from Canstatin Induces Apoptosis In Vitro and In Vivo","volume":"28","author":"Chamani","year":"2022","journal-title":"Int. J. Pept. Res. Ther."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1007\/s43152-023-00051-0","article-title":"Cancer Stem Cells Niche Regulation within the Tumor Microenvironment","volume":"5","author":"Siddiqui","year":"2024","journal-title":"Curr. Tissue Microenviron. Rep."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"23745","DOI":"10.1074\/jbc.C000186200","article-title":"RGD-Independent \u03b1v\u03b23 Binding Sites on Tumstatin","volume":"275","author":"Maeshima","year":"2000","journal-title":"J. Biol. Chem."},{"key":"ref_47","first-page":"1332","article-title":"Tumstatin 185\u2013191 Increases the Sensitivity of Non-Small Cell Lung Carcinoma Cells to Cisplatin by Blocking Proliferation, Promoting Apoptosis and Inhibiting Akt Activation","volume":"7","author":"Wang","year":"2015","journal-title":"Am. J. Transl. Res."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Brassart-Pasco, S., Senechal, K., Thevenard, J., Ramont, L., Devy, J., Di Stefano, L., Dupont-Deshorgue, A., Br\u00e9zillon, S., Feru, J., and Jazeron, J. (2012). Tetrastatin, the NC1 Domain of the \u03b14(IV) Collagen Chain: A Novel Potent Anti-Tumor Matrikine. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0029587"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"e24352","DOI":"10.1002\/pep2.24352","article-title":"Structural Modeling of Antitumoral QS-13 Peptide","volume":"116","author":"Paturel","year":"2024","journal-title":"Pept. Sci."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Lingo, J.J., Balas, M.M., Scherer, P.E., and Klein, J.C. (2025). The Role of COL6A3 in Tumorigenesis, Metastasis, Diagnosis, and Disease Management. Cancers, 17.","DOI":"10.3390\/cancers17213449"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"5779","DOI":"10.2147\/OTT.S256654","article-title":"The Biological Role of the Collagen Alpha-3 (VI) Chain and Its Cleaved C5 Domain Fragment Endotrophin in Cancer","volume":"13","author":"Wang","year":"2020","journal-title":"OncoTargets Ther."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"2447","DOI":"10.1158\/0008-5472.CAN-25-3657","article-title":"Endotrophin- and CD44-Mediated Heterotypic Signaling Mediates Tumor-Stroma Cross-Talk and Facilitates Malignant Progression in Hepatocellular Carcinoma","volume":"86","author":"Jo","year":"2026","journal-title":"Cancer Res."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1007\/s10585-021-10082-2","article-title":"Type IV Collagen as a Biomarker of Metastatic Breast Cancer","volume":"38","author":"Lindgren","year":"2021","journal-title":"Clin. Exp. Metastasis"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"240192","DOI":"10.1183\/16000617.0192-2024","article-title":"Beyond Classical Collagen: Basement Membrane Collagen IV in Age-Associated Lung Diseases","volume":"34","author":"Burgess","year":"2025","journal-title":"Eur. Respir. Rev."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"2","DOI":"10.5334\/aogh.2412","article-title":"The Global Impact of Asthma in Adult Populations","volume":"85","author":"Enilari","year":"2019","journal-title":"Ann. Glob. Health"},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Liu, L., Stephens, B., Bergman, M., May, A., and Chiang, T. (2021). Role of Collagen in Airway Mechanics. Bioengineering, 8.","DOI":"10.3390\/bioengineering8010013"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1186\/s12931-015-0225-3","article-title":"Accelerated Extracellular Matrix Turnover during Exacerbations of COPD","volume":"16","author":"Sand","year":"2015","journal-title":"Respir. Res."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"00885","DOI":"10.1183\/23120541.00885-2025","article-title":"Beyond Spirometry: Understanding COPD Origins to Support a New Diagnostic Approach","volume":"12","author":"Morelli","year":"2026","journal-title":"ERJ Open Res."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"5662","DOI":"10.4049\/jimmunol.180.8.5662","article-title":"A Novel Proteolytic Cascade Generates an Extracellular Matrix-Derived Chemoattractant in Chronic Neutrophilic Inflammation","volume":"180","author":"Gaggar","year":"2008","journal-title":"J. Immunol."},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Overbeek, S.A., Braber, S., Koelink, P.J., Henricks, P.A.J., Mortaz, E., LoTam Loi, A.T., Jackson, P.L., Garssen, J., Wagenaar, G.T.M., and Timens, W. (2013). Cigarette Smoke-Induced Collagen Destruction; Key to Chronic Neutrophilic Airway Inflammation?. PLoS ONE, 8.","DOI":"10.1371\/annotation\/0faf4c12-4fd4-474c-b5a4-16e49370aff3"},{"key":"ref_61","first-page":"32","article-title":"Proline-Glycine-Proline (PGP) and High Mobility Group Box Protein-1 (HMGB1): Potential Mediators of Cystic Fibrosis Airway Inflammation","volume":"4","author":"Gaggar","year":"2010","journal-title":"Open Respir. Med. J."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1016\/j.jcf.2010.03.001","article-title":"Alveolar Inflammation in Cystic Fibrosis","volume":"9","author":"Ulrich","year":"2010","journal-title":"J. Cyst. Fibros."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"e1500175","DOI":"10.1126\/sciadv.1500175","article-title":"The matrikine N-\u03b1-PGP couples extracellular matrix fragmentation to endothelial permeability","volume":"1","author":"Hahn","year":"2015","journal-title":"Sci. Adv."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"616","DOI":"10.3109\/1354750X.2011.620628","article-title":"A novel marker for assessment of liver matrix remodeling: An enzyme-linked immunosorbent assay (ELISA) detecting a MMP generated type I collagen neo-epitope (C1M)","volume":"16","author":"Leeming","year":"2011","journal-title":"Biomarkers"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1599","DOI":"10.31557\/APJCP.2024.25.5.1599","article-title":"Association between CTX-1 and Fibulin-1 serum levels with pathogenesis of multiple myeloma cancer","volume":"25","author":"Momeni","year":"2024","journal-title":"Asian Pac. J. Cancer Prev."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1392","DOI":"10.1158\/1055-9965.EPI-05-0909","article-title":"Alpha CTX as a biomarker of skeletal invasion of breast cancer: Immunolocalization and the load dependency of urinary excretion","volume":"15","author":"Leeming","year":"2006","journal-title":"Cancer Epidemiol. Biomark. Prev."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1026","DOI":"10.21608\/ejhm.2023.280204","article-title":"Levels of Serum Procollagen Type-1 Amino Terminal Propeptide and C-terminal Cross-linked Telopeptide of Type-1 Collagen in Children and","volume":"90","author":"Afify","year":"2023","journal-title":"Egypt. J. Hosp. Med."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1016\/j.jchf.2022.09.008","article-title":"Prediction of Left Ventricular Reverse Remodeling and Outcomes by Circulating Collagen-Derived Peptides","volume":"11","author":"Ravassa","year":"2023","journal-title":"JACC Heart Fail."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"802","DOI":"10.3889\/oamjms.2020.4798","article-title":"Role of Carboxy Terminal Propeptide of Type I and Type III Procollagen (PICP and PIIICP) Toward the Severity Degree of Mitral Valve Regurgitation in Children\u2019s Rheumatic Heart Disease","volume":"8","author":"Suwarniaty","year":"2020","journal-title":"Open Access Maced. J. Med. Sci."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"528","DOI":"10.1177\/00045632211025567","article-title":"Assessing bone formation in patients with chronic kidney disease using procollagen type I N-terminal propeptide (PINP): The choice of assay makes a difference","volume":"58","author":"Tridimas","year":"2021","journal-title":"Ann. Clin. Biochem."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1186\/1755-1536-3-5","article-title":"Procollagen type I N-terminal propeptide (PINP) is a marker for fibrogenesis in bile duct ligation-induced fibrosis in rats","volume":"3","author":"Veidal","year":"2010","journal-title":"Fibrogenesis Tissue Repair"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1016\/S8756-3282(01)00504-X","article-title":"Collagen type II C-telopeptide fragments as an index of cartilage degradation","volume":"29","author":"Christgau","year":"2001","journal-title":"Bone"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1081","DOI":"10.1002\/art.20930","article-title":"Urinary type II collagen helical peptide (HELIX-II) as a new biochemical marker of cartilage degradation in patients with osteoarthritis and rheumatoid arthritis","volume":"52","author":"Charni","year":"2005","journal-title":"Arthritis Rheum."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1605","DOI":"10.1111\/liv.15270","article-title":"An MMP-degraded and cross-linked fragment of type III collagen as a non-invasive biomarker of hepatic fibrosis resolution","volume":"42","author":"Pehrsson","year":"2022","journal-title":"Liver Int."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"3292","DOI":"10.1016\/j.yexcr.2008.08.011","article-title":"Characterization of the anti-angiogenic properties of arresten, an \u03b11\u03b21 integrin-dependent collagen-derived tumor suppressor","volume":"314","author":"Nyberg","year":"2008","journal-title":"Exp. Cell Res."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"4353","DOI":"10.1158\/0008-5472.CAN-04-3536","article-title":"Canstatin acts on endothelial and tumor cells via mitochondrial damage initiated through interaction with \u03b1v\u03b23 and \u03b1v\u03b25 integrins","volume":"65","author":"Magnon","year":"2005","journal-title":"Cancer Res."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1831","DOI":"10.2337\/diabetes.53.7.1831","article-title":"Tumstatin peptide, an inhibitor of angiogenesis, prevents glomerular hypertrophy in the early stage of diabetic nephropathy","volume":"53","author":"Yamamoto","year":"2004","journal-title":"Diabetes"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"C1294","DOI":"10.1152\/ajpcell.00391.2023","article-title":"Pentastatin, a matrikine of the collagen IV\u03b15, is a novel endogenous mediator of pulmonary endothelial dysfunction","volume":"325","author":"Mutgan","year":"2023","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"434","DOI":"10.1016\/j.bbrc.2006.12.231","article-title":"Identification of novel short peptides derived from the \u03b14, \u03b15, and \u03b16 fibrils of type IV collagen with anti-angiogenic properties","volume":"354","author":"Karagiannis","year":"2007","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"8051","DOI":"10.1074\/jbc.275.11.8051","article-title":"New functions for non-collagenous domains of human collagen type IV: Novel integrin ligands inhibiting angiogenesis and tumor growth in vivo","volume":"275","author":"Petitclerc","year":"2000","journal-title":"J. Biol. Chem."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"3485","DOI":"10.1038\/ncomms4485","article-title":"Endotrophin triggers adipose tissue fibrosis and metabolic dysfunction","volume":"5","author":"Sun","year":"2014","journal-title":"Nat. Commun."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"EVIDoa2200091","DOI":"10.1056\/EVIDoa2200091","article-title":"Endotrophin, a collagen VI formation\u2013derived peptide, in heart failure","volume":"1","author":"Chirinos","year":"2022","journal-title":"NEJM Evid."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"735","DOI":"10.1006\/bbrc.1999.0248","article-title":"Antiangiogenic activity of restin, NC10 domain of human collagen XV: Comparison to endostatin","volume":"255","author":"Ramchandran","year":"1999","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_84","first-page":"3208780","article-title":"Systematic Evaluation Meta-Analysis of the Efficacy of Recombinant Human Endostatin Combined with Gemcitabine and Cisplatin in Non-Small-Cell Lung Cancer","volume":"2022","author":"Zhang","year":"2022","journal-title":"J. Healthc. Eng."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"694","DOI":"10.4103\/ijc.IJC_1065_20","article-title":"Safety of Endostar in Combination with Chemotherapy in Patients with Cancer","volume":"61","author":"Wang","year":"2024","journal-title":"Indian J. Cancer"},{"key":"ref_86","doi-asserted-by":"crossref","unstructured":"Xu, X., Mao, W., Chen, Q., Zhuang, Q., Wang, L., Dai, J., Wang, H., and Huang, Z. (2014). Endostar, a Modified Recombinant Human Endostatin, Suppresses Angiogenesis through Inhibition of Wnt\/\u03b2-Catenin Signaling Pathway. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0107463"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"2508535","DOI":"10.1080\/15384047.2025.2508535","article-title":"Inhibitory Effect of Endostar on HIF-1 with Upregulation of MHC-I in Lung Cancer Cells","volume":"26","author":"Zhao","year":"2025","journal-title":"Cancer Biol. Ther."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"1388","DOI":"10.62347\/PJVO5304","article-title":"Endostar and Chemoradiotherapy for Advanced Cervical Cancer: Comparing Efficacy and Prognosis","volume":"17","author":"Liao","year":"2025","journal-title":"Am. J. Transl. Res."},{"key":"ref_89","doi-asserted-by":"crossref","unstructured":"Devos, H., Mina, I.K., Paradeisi, F., Makridakis, M., Tserga, A., Mokou, M., Zoidakis, J., Mischak, H., Vlahou, A., and Latosinska, A. (2025). A Naturally Occurring Urinary Collagen Type I Alpha 1-Derived Peptide Inhibits Collagen Type I-Induced Endothelial Cell Migration at Physiological Concentrations. Int. J. Mol. Sci., 26.","DOI":"10.1101\/2025.07.08.663687"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"2494","DOI":"10.1681\/ASN.2014070696","article-title":"Urine Collagen Fragments and CKD Progression\u2014The Cardiovascular Health Study","volume":"26","author":"Ix","year":"2015","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1080\/00365510500209306","article-title":"Serum Levels of Angioregulatory Mediators in Healthy Individuals Depend on Age and Physical Activity: Studies of Angiogenin, Basic Fibroblast Growth Factor, Leptin and Endostatin","volume":"65","author":"Bruserud","year":"2005","journal-title":"Scand. J. Clin. Lab. Investig."},{"key":"ref_92","doi-asserted-by":"crossref","unstructured":"Thompson, M.B., Tirupattur, S.P., Vishwakarma, N., and Katwa, L.C. (2025). Roles of VEGF and Dopamine in Aging. Cells, 14.","DOI":"10.3390\/cells14151178"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"G325","DOI":"10.1152\/ajpgi.00127.2013","article-title":"An Imbalance between VEGF and Endostatin Underlies Impaired Angiogenesis in Gastric Mucosa of Aging Rats","volume":"305","author":"Ahluwalia","year":"2013","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"15837","DOI":"10.1038\/s41598-018-34030-5","article-title":"Comparison of Efficacy and Toxicity of Bevacizumab, Endostar and Apatinib in Transgenic and Human Lung Cancer Xenograft Zebrafish Model","volume":"8","author":"Jin","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"1645","DOI":"10.1161\/CIRCULATIONAHA.109.912774","article-title":"Circulating Biomarkers of Collagen Metabolism in Cardiac Diseases","volume":"121","year":"2010","journal-title":"Circulation"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"1487","DOI":"10.1158\/1078-0432.CCR-07-1530","article-title":"Linking Antibody Fc Domain to Endostatin Significantly Improves Endostatin Half-life and Efficacy","volume":"14","author":"Lee","year":"2008","journal-title":"Clin. Cancer Res."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"901","DOI":"10.1002\/ejhf.3375","article-title":"High Variability in Assays of Blood Markers of Collagen Turnover in Cardiovascular Disease: Implications for Research and Clinical Practice","volume":"27","author":"Cleland","year":"2025","journal-title":"Eur. J. Heart Fail."}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/15\/18\/1626\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T08:22:15Z","timestamp":1788855735000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/15\/18\/1626"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,8]]},"references-count":97,"journal-issue":{"issue":"18","published-online":{"date-parts":[[2026,9]]}},"alternative-id":["cells15181626"],"URL":"https:\/\/doi.org\/10.3390\/cells15181626","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,8]]}}}