{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T04:01:14Z","timestamp":1767844874131,"version":"3.49.0"},"reference-count":60,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2014,1,24]],"date-time":"2014-01-24T00:00:00Z","timestamp":1390521600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2014,2]]},"abstract":"Midkine (MK<\/jats:styled-content>; K<\/jats:styled-content>; gene abbreviation, M<\/jats:styled-content>dk<\/jats:italic>: mus musculus, MDK<\/jats:styled-content><\/jats:italic>: homo sapiens) is a multifunctional heparin\u2010binding growth factor that regulates cell growth, survival and migration as well as anti\u2010apoptotic activity in nephrogenesis and development. Proximal tubular epithelial cells are the main sites of MK<\/jats:styled-content> expression in the kidneys. The pathophysiological roles of MK<\/jats:styled-content> are diverse, ranging from the development of acute kidney injury (AKI<\/jats:styled-content>) to the progression of chronic kidney disease, often accompanied by hypertension, renal ischaemia and diabetic nephropathy. The obvious hypertension that develops in M<\/jats:styled-content>dk+\/+<\/jats:sup><\/jats:italic> mouse models of renal ablation compared with M<\/jats:styled-content>dk\u2212\/\u2212<\/jats:sup><\/jats:italic> mice eventually leads to progressive renal failure, such as glomerular sclerosis and tubulointerstitial damage associated with elevated plasma angiotensin (A<\/jats:styled-content>ng) II<\/jats:styled-content> levels. MK<\/jats:styled-content> is also induced in the lung endothelium by oxidative stress and subsequently up\u2010regulated by ACE<\/jats:styled-content>, which hydrolyzes A<\/jats:styled-content>ng II<\/jats:styled-content> to induce further oxidative stress, thus accelerating MK<\/jats:styled-content> generation; this leads to a vicious cycle of positive feedback in the MK<\/jats:styled-content>\u2010A<\/jats:styled-content>ng II<\/jats:styled-content> pathway. Kidney\u2013lung interactions involving positive feedback between the renin\u2010angiotensin system and MK<\/jats:styled-content> might partly account for the pathogenesis of hypertension and kidney damage. MK<\/jats:styled-content> is also involved in the pathogenesis of AKI<\/jats:styled-content> and diabetic nephropathy through the recruitment of inflammatory cells. In contrast, MK<\/jats:styled-content> plays a protective role against crescentic glomerulonephritis, by down\u2010regulating plasminogen activator inhibitor\u20101. These diverse actions of MK<\/jats:styled-content> might open up new avenues for targeted approaches to treating hypertension and various renal diseases.<\/jats:p><\/jats:sec>Linked Articles<\/jats:title>This article is part of a themed section on Midkine. To view the other articles in this section visit http:\/\/dx.doi.org\/10.1111\/bph.2014.171.issue\u20104<\/jats:ext-link><\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.12418","type":"journal-article","created":{"date-parts":[[2013,10,12]],"date-time":"2013-10-12T01:02:26Z","timestamp":1381539746000},"page":"879-887","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Midkine in nephrogenesis, hypertension and kidney diseases"],"prefix":"10.1111","volume":"171","author":[{"given":"Waichi","family":"Sato","sequence":"first","affiliation":[{"name":"Department of Nephrology Nagoya University Graduate School of Medicine Nagoya Aichi Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuka","family":"Sato","sequence":"additional","affiliation":[{"name":"Department of Nephrology Nagoya University Graduate School of Medicine Nagoya Aichi Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2014,1,24]]},"reference":[{"key":"e_1_2_19_2_1","first-page":"2197","article-title":"Midkine as a novel target gene for the Wilms' tumor suppressor gene (WT1)","volume":"13","author":"Adachi Y","year":"1996","journal-title":"Oncogene"},{"key":"e_1_2_19_3_1","doi-asserted-by":"publisher","DOI":"10.1136\/thorax.55.12.981"},{"key":"e_1_2_19_4_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa011161"},{"key":"e_1_2_19_5_1","first-page":"43","article-title":"Alterations of the glomerular epithelium in acute aminonucleoside nephrosis. 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