{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T02:34:57Z","timestamp":1791513297240,"version":"4.3.4"},"reference-count":32,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"4","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation Research"],"published-print":{"date-parts":[[2025,8]]},"abstract":"<jats:sec>\n            <jats:title>BACKGROUND:<\/jats:title>\n            <jats:p>Renal fibrosis plays a key role in the progression of diabetic kidney disease (DKD). Although the renal protective effects of NPs (natriuretic peptides) were reported, the role of NPR (natriuretic peptide receptor) C in modulating renal fibrosis in DKD remains unclear.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>METHODS:<\/jats:title>\n            <jats:p>The expression and function of NPRC in DKD were investigated using human renal biopsies and a diabetic mouse model. Podocyte-specific NPRC knockout mice were developed to explore the role of NPRC in renal fibrosis. Gene and protein analyses such as histological staining, serum chemical assay, mass spectrometry analysis, ELISA, and Western blot were performed to examine the impact of NPRC deficiency on TGF-\u03b2R (transforming growth factor-\u03b2 receptor) 2 expression, recycling, small mothers against decapentaplegic homolog 2\/3 (Smad2\/3) signaling, and the overall renal structure and function.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>RESULTS:<\/jats:title>\n            <jats:p>Increased expression of NPRC was observed in both patients with DKD and DKD mice. Podocyte-specific NPRC knockout mice showed reduced glomerular fibrosis and improved podocyte injury and renal function compared with wild-type controls. Notably, NPRC knockdown resulted in decreased COL (collagen) synthesis in podocytes. Molecular biology studies revealed that NPRC deficiency led to decreased recycling and increased degradation of TGF-\u03b2R2, thus suppressing the TGF-\u03b2 (transforming growth factor-\u03b2)1\/Smad pathway.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>CONCLUSIONS:<\/jats:title>\n            <jats:p>NPRC plays a detrimental role in the progression of DKD by enhancing TGF-\u03b2R2 expression and TGF-\u03b21\/Smad signaling pathway. Podocyte-specific NPRC deficiency not only attenuates glomerular fibrosis but also improves renal function, suggesting that NPRC may serve as a promising therapeutic target for managing diabetic renal fibrosis.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/circresaha.124.325702","type":"journal-article","created":{"date-parts":[[2025,6,25]],"date-time":"2025-06-25T05:00:21Z","timestamp":1750827621000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":8,"title":["Podocyte NPRC Deficiency Attenuates Glomerular Fibrosis in Diabetic Mice"],"prefix":"10.1161","volume":"137","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8088-0252","authenticated-orcid":true,"given":"Xinlu","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Cardiology, State Key Laboratory for Innovation and Transformation of Luobing Theory, Key Laboratory of Cardiovascular Remodeling and Function Research of Ministry of Education, National Health Commission of the People\u2019s Republic of China, Chinese Academy of Medical Sciences and Shandong Province, Qilu Hospital of Shandong University (X.W., J.L., W.M., L.M., Y.L., J.S., S.C., W.Z., Y.Z., W.S., C.Z.), Cheeloo College of Medicine, Shandong University, Jinan, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingwei","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Cardiology, State Key Laboratory for Innovation and Transformation of Luobing Theory, Key Laboratory of Cardiovascular Remodeling and Function Research of Ministry of Education, National Health Commission of the People\u2019s Republic of China, Chinese Academy of Medical Sciences and Shandong Province, Qilu Hospital of Shandong University (X.W., J.L., W.M., L.M., Y.L., J.S., S.C., W.Z., Y.Z., W.S., C.Z.), Cheeloo College of Medicine, Shandong University, Jinan, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenlei","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Cardiology, State Key Laboratory for Innovation and Transformation of Luobing Theory, Key Laboratory of Cardiovascular Remodeling and Function Research of Ministry of Education, National Health Commission of the People\u2019s Republic of China, Chinese Academy of Medical Sciences and Shandong Province, Qilu Hospital of Shandong University (X.W., J.L., W.M., L.M., Y.L., J.S., S.C., W.Z., Y.Z., W.S., C.Z.), Cheeloo College of Medicine, Shandong University, Jinan, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-6640-3654","authenticated-orcid":true,"given":"Linlin","family":"Meng","sequence":"additional","affiliation":[{"name":"Department of Cardiology, State Key Laboratory for Innovation and Transformation of Luobing Theory, Key Laboratory of Cardiovascular Remodeling and Function Research of Ministry of Education, National Health Commission of the People\u2019s Republic of China, Chinese Academy of Medical Sciences and Shandong Province, Qilu Hospital of Shandong University (X.W., J.L., W.M., L.M., Y.L., J.S., S.C., W.Z., Y.Z., W.S., C.Z.), Cheeloo College of Medicine, Shandong University, Jinan, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Cardiology, State Key Laboratory for Innovation and Transformation of Luobing Theory, Key Laboratory of Cardiovascular Remodeling and Function Research of Ministry of Education, National Health Commission of the People\u2019s Republic of China, Chinese Academy of Medical Sciences and Shandong Province, Qilu Hospital of Shandong University (X.W., J.L., W.M., L.M., Y.L., J.S., S.C., W.Z., Y.Z., W.S., C.Z.), Cheeloo College of Medicine, Shandong University, Jinan, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiawei","family":"Song","sequence":"additional","affiliation":[{"name":"Department of Cardiology, State Key Laboratory for Innovation and Transformation of Luobing Theory, Key Laboratory of Cardiovascular Remodeling and Function Research of Ministry of Education, National Health Commission of the People\u2019s Republic of China, Chinese Academy of Medical Sciences and Shandong Province, Qilu Hospital of Shandong University (X.W., J.L., W.M., L.M., Y.L., J.S., S.C., W.Z., Y.Z., W.S., C.Z.), Cheeloo College of Medicine, Shandong University, Jinan, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-1476-1226","authenticated-orcid":true,"given":"Sizhe","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Cardiology, State Key Laboratory for Innovation and Transformation of Luobing Theory, Key Laboratory of Cardiovascular Remodeling and Function Research of Ministry of Education, National Health Commission of the People\u2019s Republic of China, Chinese Academy of Medical Sciences and Shandong Province, Qilu Hospital of Shandong University (X.W., J.L., W.M., L.M., Y.L., J.S., S.C., W.Z., Y.Z., W.S., C.Z.), Cheeloo College of Medicine, Shandong University, Jinan, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junhui","family":"Zhen","sequence":"additional","affiliation":[{"name":"Department of Pathology, School of Basic Medical Sciences, Shandong University, Jinan, China (J.Z.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1119-8334","authenticated-orcid":true,"given":"Xiao","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Physiology, Key Laboratory Experimental Teratology of the Ministry of Education, School of Basic Medical Sciences (X.Y.), Cheeloo College of Medicine, Shandong University, Jinan, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0491-5585","authenticated-orcid":true,"given":"Bo","family":"Xi","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, School of Public Health (B.X.), Cheeloo College of Medicine, Shandong University, Jinan, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4670-3727","authenticated-orcid":true,"given":"Feng","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine, Chest Pain Center, Shandong Provincial Clinical Research Center for Emergency and Critical Care Medicine, Qilu Hospital of Shandong University, Jinan, China (F.X.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9416-6540","authenticated-orcid":true,"given":"Wencheng","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Cardiology, State Key Laboratory for Innovation and Transformation of Luobing Theory, Key Laboratory of Cardiovascular Remodeling and Function Research of Ministry of Education, National Health Commission of the People\u2019s Republic of China, Chinese Academy of Medical Sciences and Shandong Province, Qilu Hospital of Shandong University (X.W., J.L., W.M., L.M., Y.L., J.S., S.C., W.Z., Y.Z., W.S., C.Z.), Cheeloo College of Medicine, Shandong University, Jinan, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4432-6144","authenticated-orcid":true,"given":"Yun","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Cardiology, State Key Laboratory for Innovation and Transformation of Luobing Theory, Key Laboratory of Cardiovascular Remodeling and Function Research of Ministry of Education, National Health Commission of the People\u2019s Republic of China, Chinese Academy of Medical Sciences and Shandong Province, Qilu Hospital of Shandong University (X.W., J.L., W.M., L.M., Y.L., J.S., S.C., W.Z., Y.Z., W.S., C.Z.), Cheeloo College of Medicine, Shandong University, Jinan, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6114-0443","authenticated-orcid":true,"given":"Wenhai","family":"Sui","sequence":"additional","affiliation":[{"name":"Department of Cardiology, State Key Laboratory for Innovation and Transformation of Luobing Theory, Key Laboratory of Cardiovascular Remodeling and Function Research of Ministry of Education, National Health Commission of the People\u2019s Republic of China, Chinese Academy of Medical Sciences and Shandong Province, Qilu Hospital of Shandong University (X.W., J.L., W.M., L.M., Y.L., J.S., S.C., W.Z., Y.Z., W.S., C.Z.), Cheeloo College of Medicine, Shandong University, Jinan, 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