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foundation","award":["ANR-15-RHUS-0004"],"award-info":[{"award-number":["ANR-15-RHUS-0004"]}]},{"name":"Uehara memorial foundation","award":["REIN\/NgalPA-2017\/2018"],"award-info":[{"award-number":["REIN\/NgalPA-2017\/2018"]}]},{"name":"Uehara memorial foundation","award":["ANR-19-CE14-0013"],"award-info":[{"award-number":["ANR-19-CE14-0013"]}]},{"name":"Uehara memorial foundation","award":["CP13\/00221"],"award-info":[{"award-number":["CP13\/00221"]}]},{"name":"Uehara memorial foundation","award":["PI21\/00280"],"award-info":[{"award-number":["PI21\/00280"]}]},{"name":"Cell Science Research Foundation","award":["ANR-15-RHUS-0004"],"award-info":[{"award-number":["ANR-15-RHUS-0004"]}]},{"name":"Cell Science Research Foundation","award":["REIN\/NgalPA-2017\/2018"],"award-info":[{"award-number":["REIN\/NgalPA-2017\/2018"]}]},{"name":"Cell Science Research Foundation","award":["ANR-19-CE14-0013"],"award-info":[{"award-number":["ANR-19-CE14-0013"]}]},{"name":"Cell Science Research Foundation","award":["CP13\/00221"],"award-info":[{"award-number":["CP13\/00221"]}]},{"name":"Cell Science Research Foundation","award":["PI21\/00280"],"award-info":[{"award-number":["PI21\/00280"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The beneficial effects of mineralocorticoid receptor (MR) antagonists (MRAs) for various kidney diseases are established. However, the underlying mechanisms of kidney injury induced by MR activation remain to be elucidated. We recently reported aldosterone-induced enhancement of proteoglycan expression in mitral valve interstitial cells and its association with fibromyxomatous valvular disorder. As the expression of certain proteoglycans is elevated in several kidney diseases, we hypothesized that proteoglycans mediate kidney injury in the context of aldosterone\/MR pathway activation. We evaluated the proteoglycan expression and tissue injury in the kidney and isolated glomeruli of uninephrectomy\/aldosterone\/salt (NAS) mice. The MRA eplerenone was administered to assess the role of the MR pathway. We investigated the direct effects of biglycan, one of the proteoglycans, on macrophages using isolated macrophages. The kidney samples from NAS-treated mice showed enhanced fibrosis and increased expression of biglycan accompanying glomerular macrophage infiltration and enhanced expression of TNF-\u03b1, iNOS, Nox2, CCL3 (C-C motif chemokine ligand 3), and phosphorylated NF-\u03baB. Eplerenone blunted these changes. Purified biglycan stimulated macrophages to express TNF-\u03b1, iNOS, Nox2, and CCL3. This was prevented by a toll-like receptor 4 (TLR4) or NF-\u03baB inhibitor, indicating that biglycan stimulation is dependent on the TLR4\/NF-\u03baB pathway. We identified the proteoglycan biglycan as a novel target of MR involved in MR-induced glomerular injury and macrophage infiltration via a biglycan\/TLR4\/NF-\u03baB\/CCL3 cascade.<\/jats:p>","DOI":"10.3390\/ijms23126680","type":"journal-article","created":{"date-parts":[[2022,6,15]],"date-time":"2022-06-15T22:17:01Z","timestamp":1655331421000},"page":"6680","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Biglycan Is a Novel Mineralocorticoid Receptor Target Involved in Aldosterone\/Salt-Induced Glomerular Injury"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2485-7028","authenticated-orcid":false,"given":"Toshifumi","family":"Nakamura","sequence":"first","affiliation":[{"name":"Centre de Recherche des Cordeliers, INSERM, Sorbonne Universit\u00e9, Universit\u00e9 de Paris, 75006 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin","family":"Bonnard","sequence":"additional","affiliation":[{"name":"Centre de Recherche des Cordeliers, INSERM, Sorbonne Universit\u00e9, Universit\u00e9 de Paris, 75006 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0867-1277","authenticated-orcid":false,"given":"Roberto","family":"Palacios-Ramirez","sequence":"additional","affiliation":[{"name":"Centre de Recherche des Cordeliers, INSERM, Sorbonne Universit\u00e9, Universit\u00e9 de Paris, 75006 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amaya","family":"Fern\u00e1ndez-Celis","sequence":"additional","affiliation":[{"name":"Cardiovascular Translational Research, Navarrabiomed (Miguel Servet Foundation), Instituto de Investigaci\u00f3n Sanitaria de Navarra (IdiSNA), 31008 Pamplona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fr\u00e9d\u00e9ric","family":"Jaisser","sequence":"additional","affiliation":[{"name":"Centre de Recherche des Cordeliers, INSERM, Sorbonne Universit\u00e9, Universit\u00e9 de Paris, 75006 Paris, France"},{"name":"INSERM, Clinical Investigation Centre 1433, French-Clinical Research Infrastructure Network (F-CRIN) INI-CRCT (Cardiovascular and Renal Clinical Trialists), 54500 Nancy, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalia","family":"L\u00f3pez-Andr\u00e9s","sequence":"additional","affiliation":[{"name":"Cardiovascular Translational Research, Navarrabiomed (Miguel Servet Foundation), Instituto de Investigaci\u00f3n Sanitaria de Navarra (IdiSNA), 31008 Pamplona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,6,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1679","DOI":"10.1681\/ASN.2006090975","article-title":"Impairment of sodium balance in mice deficient in renal principal cell mineralocorticoid receptor","volume":"18","author":"Ronzaud","year":"2007","journal-title":"J. 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