{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T20:48:59Z","timestamp":1786135739951,"version":"build-2736575974"},"reference-count":41,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"8","funder":[{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["R01HL117062"],"award-info":[{"award-number":["R01HL117062"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["R01DK124901"],"award-info":[{"award-number":["R01DK124901"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["JASN"],"published-print":{"date-parts":[[2022,8]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      The proximal tubules play a critical role in phosphate (Pi) homeostasis by reabsorbing Pi\n                      <jats:italic toggle=\"yes\">via<\/jats:italic>\n                      sodium-dependent Pi cotransporters. NPT2A is a major proximal-specific Pi cotransporter, whose expression is regulated by circulating hormones, such as parathyroid hormone (PTH) and fibroblast growth factor 23 (FGF23). In this study, we aimed to find a novel regulator in Pi homeostasis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Using RNA-seq and RT-qPCR analysis, we identified proximal tubule cell\u2013enriched genes. We next used RNAi screening of the identified proximal tubular cell\u2013enriched genes to identify a novel proximal tubule\u2013specific gene that contributes to FGF23- and PTH-mediated inhibition of Pi uptake and NPT2 reduction. We created mice lacking this novel regulator of Pi homeostasis to examine whether the novel regulator contributes to Pi homeostasis\n                      <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We identified 54 kidney-enriched genes, 19 of which are expressed in renal primary proximal tubule cells. One of the proximal tubule\u2013specific genes, TMEM174, interacted with NPT2A, and its knockdown blocked the reduction of NPT2A protein by FGF23 and PTH treatments in human and opossum proximal tubule cells. TMEM174 KO mice had significantly increased levels of serum Pi, FGF23, and PTH, resulting in vascular calcification.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>TMEM174 is a novel regulator of Pi homeostasis that interacts with NPT2A.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1681\/asn.2021121578","type":"journal-article","created":{"date-parts":[[2022,5,11]],"date-time":"2022-05-11T02:05:10Z","timestamp":1652234710000},"page":"1477-1486","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":16,"title":["Targeted Disruption of a Proximal Tubule\u2013Specific TMEM174 Gene in Mice Causes Hyperphosphatemia and Vascular Calcification"],"prefix":"10.1681","volume":"33","author":[{"given":"Shinobu","family":"Miyazaki-Anzai","sequence":"first","affiliation":[{"name":"Division of Renal Diseases and Hypertension, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Audrey L.","family":"Keenan","sequence":"additional","affiliation":[{"name":"Division of Renal Diseases and Hypertension, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Judith","family":"Blaine","sequence":"additional","affiliation":[{"name":"Division of Renal Diseases and Hypertension, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Makoto","family":"Miyazaki","sequence":"additional","affiliation":[{"name":"Division of Renal Diseases and Hypertension, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, 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