{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T14:25:43Z","timestamp":1791901543096,"version":"4.3.4"},"reference-count":54,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"9","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JASN"],"published-print":{"date-parts":[[2018,9]]},"abstract":"\n Background<\/jats:title>\n Autosomal-dominant polycystic kidney disease (ADPKD) is the leading inherited renal disease worldwide. The proproliferative function of macrophages is associated with late-stage cyst enlargement in mice with PKD; however, the way in which macrophages act on cyst-lining epithelial cells (CLECs) has not been well elucidated.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n We generated a rapid-onset PKD mouse model by inactivating\n Pkd1<\/jats:italic>\n on postnatal day 10 (P10) and compared cell proliferation and differential gene expression in kidney tissues of the PKD mice and wild-type (WT) littermates.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n The cystic phenotype was dominant from P18. A distinct peak in cell proliferation in polycystic kidneys during P22\u2013P30 was closely related to late-stage cyst growth. Comparisons of gene expression profiles in kidney tissues at P22 and P30 in PKD and WT mice revealed that arginine metabolism was significantly activated; 204 differentially expressed genes (DEGs), including\n Arg1<\/jats:italic>\n , an arginine metabolism\u2013associated gene, were identified in late-stage polycystic kidneys. The\n Arg1<\/jats:italic>\n -encoded protein, arginase-1 (ARG1), was predominantly expressed in macrophages in a time-dependent manner. Multiple-stage macrophage depletion verified that macrophages expressing high ARG1 levels accounted for late-stage cyst enlargement, and inhibiting ARG1 activity significantly retarded cyst growth and effectively lowered the proliferative indices in polycystic kidneys.\n In vitro<\/jats:italic>\n experiments revealed that macrophages stimulated CLEC proliferation, and that L\u2013lactic acid, primarily generated by CLECs, significantly upregulated ARG1 expression and increased polyamine synthesis in macrophages.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n Interactions between macrophages and CLECs promote cyst growth. ARG1 is a key molecule involved in this process and is a potential therapeutic target to help delay ADPKD progression.<\/jats:p>\n <\/jats:sec>","DOI":"10.1681\/asn.2018010074","type":"journal-article","created":{"date-parts":[[2018,7,24]],"date-time":"2018-07-24T17:03:57Z","timestamp":1532451837000},"page":"2310-2325","source":"Crossref","is-referenced-by-count":65,"title":["Interactions between Macrophages and Cyst-Lining Epithelial Cells Promote Kidney Cyst Growth in Pkd1-Deficient Mice"],"prefix":"10.1681","volume":"29","author":[{"given":"Yang","family":"Yang","sequence":"first","affiliation":[{"name":"Division of Nephrology, Kidney Institution of Chinese People's Liberation Army (PLA), Chang Zheng Hospital, The Second Military Medical University, Shanghai, China;"},{"name":"Division of Nephrology, Kidney Diagnostic and Therapeutic Center of PLA, Beidaihe Sanatorium of PLA, Qinhuangdao, China; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meihan","family":"Chen","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Kidney Institution of Chinese People's Liberation Army (PLA), Chang Zheng Hospital, The Second Military Medical University, Shanghai, China;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Zhou","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Kidney Institution of Chinese People's Liberation Army (PLA), Chang Zheng Hospital, The Second Military Medical University, Shanghai, China;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiayi","family":"Lv","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Kidney Institution of Chinese People's Liberation Army (PLA), Chang Zheng Hospital, The Second Military Medical University, Shanghai, 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