{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T18:09:51Z","timestamp":1790359791769,"version":"4.1.0"},"reference-count":55,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2018,3,25]],"date-time":"2018-03-25T00:00:00Z","timestamp":1521936000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100007225","name":"Ministry of Science and Technology","doi-asserted-by":"publisher","award":["MOST 105\u20102628\u2010B\u2010016\u2010005"],"award-info":[{"award-number":["MOST 105\u20102628\u2010B\u2010016\u2010005"]}],"id":[{"id":"10.13039\/100007225","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007225","name":"Ministry of Science and Technology","doi-asserted-by":"publisher","award":["MOST 106\u20102314\u2010B\u2010016\u2010030"],"award-info":[{"award-number":["MOST 106\u20102314\u2010B\u2010016\u2010030"]}],"id":[{"id":"10.13039\/100007225","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Pineal Research"],"published-print":{"date-parts":[[2018,8]]},"abstract":"Abstract<\/jats:title>Membranous nephropathy (MN<\/jats:styled-content>), a type of glomerular nephritis, is one of the most common causes of nephrotic syndrome in adults. Although it is known that melatonin plays a protective role in MN<\/jats:styled-content>, the role of melatonin receptors in the pathophysiology of MN<\/jats:styled-content> is unclear. Using an experimental MN<\/jats:styled-content> model and clinical MN<\/jats:styled-content> specimens, we studied melatonin receptor expression and found that melatonin receptor 1A (MTNR<\/jats:styled-content>1A) expression was significantly downregulated in renal tubular epithelial cells. Molecular studies showed that the transcription factor pituitary homeobox\u20101 (PITX<\/jats:styled-content>1) promoted MTNR<\/jats:styled-content>1A<\/jats:italic> expression via direct binding to its promoter. Treatment of a human tubular cell line with albumin to induce injury resulted in the stable reduction in MTNR<\/jats:styled-content>1A and PITX<\/jats:styled-content>1 expression. PITX<\/jats:styled-content>1 levels were significantly downregulated in tubular epithelial cells from mice MN<\/jats:styled-content> kidneys and MN<\/jats:styled-content> renal specimens. Knockdown of MTNR<\/jats:styled-content>1A, PITX<\/jats:styled-content>1, or cyclic adenosine monophosphate\u2010responsive element\u2010binding protein (CREB<\/jats:styled-content>) decreased E\u2010cadherin (CDH<\/jats:styled-content>1) expression, but upregulated Per2 and \u03b1\u2010smooth muscle actin (\u03b1SMA<\/jats:styled-content>) expression. Blockade of the MTNR<\/jats:styled-content>1A receptor with luzindole in MN<\/jats:styled-content> mice further impaired renal function; this was accompanied by CDH<\/jats:styled-content>1 downregulation and Per2 and \u03b1SMA<\/jats:styled-content> upregulation. Together, our results suggest that in injured tissue, decreased PITX<\/jats:styled-content>1 expression at the MTNR<\/jats:styled-content>1A promoter regions leads to decreased levels of MTNR<\/jats:styled-content>1A in renal tubular epithelial cells, which increases the future risk of MN<\/jats:styled-content>.<\/jats:p>","DOI":"10.1111\/jpi.12482","type":"journal-article","created":{"date-parts":[[2018,2,26]],"date-time":"2018-02-26T15:32:31Z","timestamp":1519659151000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Role of melatonin receptor 1A and pituitary homeobox\u20101 coexpression in protecting tubular epithelial cells in membranous nephropathy"],"prefix":"10.1111","volume":"65","author":[{"given":"Yen\u2010Sung","family":"Huang","sequence":"first","affiliation":[{"name":"Institute of Biomedical Sciences Academia Sinica Taipei 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