{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T13:20:39Z","timestamp":1787318439904,"version":"build-2736575974"},"reference-count":56,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2019,9,10]],"date-time":"2019-09-10T00:00:00Z","timestamp":1568073600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Patients with a relapse of idiopathic nephrotic syndrome have significantly increased levels of serum complement component 5a (C5a), and proteinuria has been noted in mice treated with C5a via changes in permeability of kidney endothelial cells (KECs) in established animal models. However, the apoptosis of KECs treated with high concentrations of C5a has also been observed. As mitochondrial damage is known to be important in cell apoptosis, the aim of this study was to examine the association between C5a-induced mouse KEC apoptosis and mitochondrial damage. Mouse KECs were isolated and treated with different concentrations of C5a. Cell viability assays showed that a high-concentration mouse recombinant protein C5a (rmC5a) treatment reduced mouse KEC growth. Cell cycle phase analysis, including apoptosis (sub-G1 phase) showed an increased percentage of the subG1 phase with a high-concentration rmC5a treatment. Cytochrome c and caspase 3\/9 activities were significantly induced in the mouse KECs after a high-dose rmC5a (50 ng\/mL) treatment, and this was rescued by pretreatment with the C5a receptor (C5aR) inhibitor (W-54011) and N-acetylcysteine (NAC). Reactive oxygen species (ROS) formation was detected in C5a-treated mouse KECs; however, W-54011 or NAC pretreatment inhibited high-dose rmC5a-induced ROS formation and also reduced cytochrome c release, apoptotic cell formation, and apoptotic DNA fragmentation. These factors determined the apoptosis of mouse KECs treated with high-dose C5a through C5aR and subsequently led to apoptosis via ROS regeneration and cytochrome c release. The results showed that high concentrations of C5a induced mouse KEC apoptosis via a C5aR\/ROS\/mitochondria-dependent pathway. These findings may shed light on the potential mechanism of glomerular sclerosis, a process in idiopathic nephrotic syndrome causing renal function impairment.<\/jats:p>","DOI":"10.3390\/ijms20184465","type":"journal-article","created":{"date-parts":[[2019,9,10]],"date-time":"2019-09-10T10:52:26Z","timestamp":1568112746000},"page":"4465","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["High Concentration of C5a-Induced Mitochondria-Dependent Apoptosis in Murine Kidney Endothelial Cells"],"prefix":"10.3390","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3967-9412","authenticated-orcid":false,"given":"I-Jung","family":"Tsai","sequence":"first","affiliation":[{"name":"Department of Pediatrics, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei 100, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei-Chou","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Pathology, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei 100, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yao-Hsu","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei 100, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu-Lin","family":"Tseng","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei 100, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8153-1441","authenticated-orcid":false,"given":"Yen-Hung","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei 100, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chia-Hung","family":"Chou","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei 100, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong-Kwei","family":"Tsau","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei 100, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,9,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"918","DOI":"10.1172\/JCI113403","article-title":"Differential effects of the complement peptides, C5a and C5a des Arg on human basophil and lung mast cell histamine release","volume":"81","author":"Schulman","year":"1988","journal-title":"J. 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