{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T13:34:37Z","timestamp":1790948077317,"version":"4.1.0"},"reference-count":61,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2020,5,17]],"date-time":"2020-05-17T00:00:00Z","timestamp":1589673600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006107","name":"Gil Medical Center, Gachon University","doi-asserted-by":"publisher","award":["2017-13"],"award-info":[{"award-number":["2017-13"]}],"id":[{"id":"10.13039\/501100006107","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["2019R1F1A1057630"],"award-info":[{"award-number":["2019R1F1A1057630"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Vascular calcification (VC) is commonly associated with bone loss in patients with chronic kidney disease (CKD). The Wingless-related integration site (Wnt) regulates osteoblast activation through canonical signaling pathways, but the common pathophysiology of these pathways during VC and bone loss has not been identified. A rat model of adenine-induced CKD with VC was used in this study. The rats were fed 0.75% adenine (2.5% protein, 0.92% phosphate) with or without intraperitoneal injection of calcitriol (0.08 \u00b5g\/kg\/day) for 4 weeks. Angiotensin II (3 \u00b5M)-induced VC was achieved in high phosphate medium (3 mM) through its effect on vascular smooth muscle cells (VSMCs). In an mRNA profiler polymerase chain reaction assay of the Wnt signaling pathway, secreted frizzled-related protein 5 (sFRP5) levels were significantly decreased in the CKD rat model compared with the control group. The repression of sFRP5 on VSMC trans-differentiation was mediated through Rho\/Rho-associated coiled coil containing protein kinase (ROCK) and c-Jun N-terminal kinase (JNK) pathways activated by Wnt3a. In a proof of concept study conducted with patients with CKD, serum sFRP5 concentrations were significantly lower in subjects with VC than in those without VC. Our findings suggest that repression of sFRP5 is associated with VC in the CKD environment via activation of the noncanonical Wnt pathway, and thus that sFRP5 might be a novel therapeutic target for VC in CKD.<\/jats:p>","DOI":"10.3390\/ijms21103539","type":"journal-article","created":{"date-parts":[[2020,5,18]],"date-time":"2020-05-18T02:43:42Z","timestamp":1589769822000},"page":"3539","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Reduction of Secreted Frizzled-Related Protein 5 Drives Vascular Calcification through Wnt3a-Mediated Rho\/ROCK\/JNK Signaling in Chronic Kidney Disease"],"prefix":"10.3390","volume":"21","author":[{"given":"Yun Jung","family":"Oh","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, Graduate School of Medicine, Gachon University, Incheon 21936, Korea"},{"name":"Division of Nephrology, Department of Internal Medicine, Cheju Halla General Hospital, Jeju 63127, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyunsook","family":"Kim","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Gachon Advanced Institute for Health Sciences and Technology, Incheon 21999, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ae Jin","family":"Kim","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Internal Medicine, Gil Medical Center, Incheon 21565, Korea"},{"name":"Division of Nephrology, Department of Internal Medicine, College of Medicine, Gachon University, Incheon 21565, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Han","family":"Ro","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Internal Medicine, Gil Medical Center, Incheon 21565, Korea"},{"name":"Division of Nephrology, Department of Internal Medicine, College of Medicine, Gachon University, Incheon 21565, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jae Hyun","family":"Chang","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Internal Medicine, Gil Medical Center, Incheon 21565, Korea"},{"name":"Division of Nephrology, Department of Internal Medicine, College of Medicine, Gachon University, Incheon 21565, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyun Hee","family":"Lee","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Internal Medicine, Gil Medical Center, Incheon 21565, Korea"},{"name":"Division of Nephrology, Department of Internal Medicine, College of Medicine, Gachon University, Incheon 21565, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wookyung","family":"Chung","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Internal Medicine, Gil Medical Center, Incheon 21565, Korea"},{"name":"Division of Nephrology, Department of Internal Medicine, College of Medicine, Gachon University, Incheon 21565, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1166-4932","authenticated-orcid":false,"given":"Hee-Sook","family":"Jun","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Gachon University, Incheon 21936, Korea"},{"name":"Lee Gil Ya Cancer and Diabetes Institute, Gachon University, Incheon 21999, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1271-8012","authenticated-orcid":false,"given":"Ji Yong","family":"Jung","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Gachon Advanced Institute for Health Sciences and Technology, Incheon 21999, Korea"},{"name":"Division of Nephrology, Department of Internal Medicine, Gil Medical Center, Incheon 21565, Korea"},{"name":"Division of Nephrology, Department of Internal Medicine, College of Medicine, Gachon University, Incheon 21565, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,5,17]]},"reference":[{"key":"ref_1","unstructured":"Kidney Disease: Improving Global Outcomes (KDIGO) CKD-MBD Work Group (2009). 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