{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T23:38:09Z","timestamp":1780443489641,"version":"3.54.1"},"reference-count":122,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,1,5]],"date-time":"2026-01-05T00:00:00Z","timestamp":1767571200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cardiovasc. Med."],"abstract":"<jats:p>Kallistatin, a multifunctional serine protease inhibitor, is widely distributed with tissue-specific effects. It may serve as a new diagnostic biomarker and therapeutic target for human diseases. Through binding to its two structural elements and specific receptors, it regulates differential signaling cascades, and thus has a wide spectrum of biological functions. In cardiovascular diseases like hypertension, atherosclerosis, and heart failure, it exerts protective effects by improving endothelial function, anti-inflammation, and regulating lipid metabolism. In liver diseases, high hepatic expression correlates with nonalcoholic fatty liver disease, while decreased serum levels indicate severe cirrhosis or liver fibrosis. In metabolic diseases, it regulates insulin resistance, glucose metabolism, angiogenesis and inflammation. In inflammatory diseases, its role is dual: it attenuates inflammation in rheumatoid arthritis, sepsis, etc., but exacerbates chronic rhinosinusitis and autoimmune uveitis by promoting inflammatory cytokines secretion. In cancer, it inhibits tumor cell proliferation, angiogenesis, and metastasis, with lower tumor tissue expression linked to cancer development. Kallistatin also serves as a potential biomarker for chronic kidney disease, preterm birth, neurodegenerative diseases, and other diseases. This review synthesizes current knowledge on kallistatin's mechanisms in organ injury and repair, emphasizes its therapeutic potential across disease contexts, and discusses challenges and future directions for clinical translation, including organ-targeted strategies and combination therapies.<\/jats:p>","DOI":"10.3389\/fcvm.2025.1701235","type":"journal-article","created":{"date-parts":[[2026,1,5]],"date-time":"2026-01-05T05:29:19Z","timestamp":1767590959000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["The multifaceted role of kallistatin in human diseases: mechanistic insights and translational potential"],"prefix":"10.3389","volume":"12","author":[{"given":"Minrong","family":"Yu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanqing","family":"Feng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiyan","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suchun","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,1,5]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"38457","DOI":"10.1074\/jbc.M005605200","article-title":"Roles of the P1, P2, and P3 residues in determining inhibitory specificity of kallistatin toward human tissue kallikrein","volume":"275","author":"Chen","year":"2000","journal-title":"J Biol Chem"},{"key":"B2","doi-asserted-by":"publisher","first-page":"237","DOI":"10.1016\/S0167-4838(00)00044-3","article-title":"Reactive-site specificity of human kallistatin toward tissue kallikrein probed by site-directed mutagenesis","volume":"1479","author":"Chen","year":"2000","journal-title":"Biochim Biophys Acta"},{"key":"B3","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/978-1-4615-9546-5_1","article-title":"Human kallistatin, a new tissue kallikrein- binding protein: purification and characterization","author":"Wang","year":"1989","journal-title":"Adv Exp Med Biol"},{"key":"B4","doi-asserted-by":"publisher","first-page":"200","DOI":"10.1186\/s13054-015-0919-4","article-title":"Kallistatin treatment attenuates lethality and organ injury in mouse models of established sepsis","volume":"19","author":"Li","year":"2015","journal-title":"Crit Care"},{"key":"B5","doi-asserted-by":"publisher","first-page":"612","DOI":"10.1016\/S0022-2143(96)90152-3","article-title":"Kallistatin, a novel human tissue kallikrein inhibitor: levels in body fluids, blood cells, and tissues in health and disease","volume":"127","author":"Chao","year":"1996","journal-title":"J Lab Clin Med"},{"key":"B6","doi-asserted-by":"publisher","first-page":"189273","DOI":"10.1016\/j.bbcan.2025.189273","article-title":"The comparison of pathogenic role and mechanism of kallistatin and PEDF in tumors","volume":"1880","author":"Lyu","year":"2025","journal-title":"Biochim BiophysActa Rev Cancer"},{"key":"B7","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1186\/1479-7364-7-22","article-title":"Update of the human and mouse SERPIN gene superfamily","volume":"7","author":"Heit","year":"2013","journal-title":"Hum Genomics"},{"key":"B8","doi-asserted-by":"publisher","first-page":"24498","DOI":"10.1016\/S0021-9258(20)80553-5","article-title":"Kallistatin: a novel human serine proteinase inhibitor. 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