{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,17]],"date-time":"2026-04-17T20:05:16Z","timestamp":1776456316883,"version":"3.51.2"},"reference-count":62,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2020,2,13]],"date-time":"2020-02-13T00:00:00Z","timestamp":1581552000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["FDN-154303"],"award-info":[{"award-number":["FDN-154303"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100002253","name":"Netherland-America Foundation","doi-asserted-by":"publisher","award":["FES0908"],"award-info":[{"award-number":["FES0908"]}],"id":[{"id":"10.13039\/100002253","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Epigenomes"],"abstract":"<jats:p>In the pathophysiologic setting of acute and chronic kidney injury, the excessive activation and recruitment of blood-borne monocytes prompts their differentiation into inflammatory macrophages, a process that leads to progressive glomerulosclerosis and interstitial fibrosis. Importantly, this differentiation of monocytes into macrophages requires the meticulous coordination of gene expression at both the transcriptional and post-transcriptional level. The transcriptomes of these cells are ultimately determined by RNA-binding proteins such as QUAKING (QKI), that define their pre-mRNA splicing and mRNA transcript patterns. Using two mouse models, namely (1) quaking viable mice (qkv) and (2) the conditional deletion in the myeloid cell lineage using the lysozyme 2-Cre (QKIFL\/FL;LysM-Cre mice), we demonstrate that the abrogation of QKI expression in the myeloid cell lineage reduces macrophage infiltration following kidney injury induced by unilateral urethral obstruction (UUO). The qkv and QKIFL\/FL;LysM-Cre mice both showed significant diminished interstitial collagen deposition and fibrosis in the UUO-damaged kidney, as compared to wild-type littermates. We show that macrophages isolated from QKIFL\/FL;LysM-Cre mice are associated with defects in pre-mRNA splicing. Our findings demonstrate that reduced expression of the alternative splice regulator QKI in the cells of myeloid lineage attenuates renal interstitial fibrosis, suggesting that inhibition of this splice regulator may be of therapeutic value for certain kidney diseases.<\/jats:p>","DOI":"10.3390\/epigenomes4010002","type":"journal-article","created":{"date-parts":[[2020,2,14]],"date-time":"2020-02-14T10:09:57Z","timestamp":1581674997000},"page":"2","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Targeting the RNA-Binding Protein QKI in Myeloid Cells Ameliorates Macrophage-Induced Renal Interstitial Fibrosis"],"prefix":"10.3390","volume":"4","author":[{"given":"Ruben G.","family":"de Bruin","sequence":"first","affiliation":[{"name":"Einthoven Laboratory for Experimental Vascular Medicine, Division of Nephrology, Department of Internal Medicine, Leiden University Medical Center, Albinusdreef 2, C7-36, PO Box 9600, 2300RC Leiden, The Netherlands"},{"name":"Segal Cancer Center, Lady Davis Institute for Medical Research and Gerald Bronfman Department of Oncology and Departments of Biochemistry, Human Genetics and Medicine, McGill University, Montr\u00e9al, QC H3T 1E2, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gillian","family":"Vogel","sequence":"additional","affiliation":[{"name":"Segal Cancer Center, Lady Davis Institute for Medical Research and Gerald Bronfman Department of Oncology and Departments of Biochemistry, Human Genetics and Medicine, McGill University, Montr\u00e9al, QC H3T 1E2, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jurrien","family":"Prins","sequence":"additional","affiliation":[{"name":"Einthoven Laboratory for Experimental Vascular Medicine, Division of Nephrology, Department of Internal Medicine, Leiden University Medical Center, Albinusdreef 2, C7-36, PO Box 9600, 2300RC Leiden, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jacques M. J. G.","family":"Duijs","sequence":"additional","affiliation":[{"name":"Einthoven Laboratory for Experimental Vascular Medicine, Division of Nephrology, Department of Internal Medicine, Leiden University Medical Center, Albinusdreef 2, C7-36, PO Box 9600, 2300RC Leiden, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6438-4133","authenticated-orcid":false,"given":"Roel","family":"Bijkerk","sequence":"additional","affiliation":[{"name":"Einthoven Laboratory for Experimental Vascular Medicine, Division of Nephrology, Department of Internal Medicine, Leiden University Medical Center, Albinusdreef 2, C7-36, PO Box 9600, 2300RC Leiden, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1479-1934","authenticated-orcid":false,"given":"Hendrik J. P.","family":"van der Zande","sequence":"additional","affiliation":[{"name":"Einthoven Laboratory for Experimental Vascular Medicine, Division of Nephrology, Department of Internal Medicine, Leiden University Medical Center, Albinusdreef 2, C7-36, PO Box 9600, 2300RC Leiden, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2429-7462","authenticated-orcid":false,"given":"Janine M.","family":"van Gils","sequence":"additional","affiliation":[{"name":"Einthoven Laboratory for Experimental Vascular Medicine, Division of Nephrology, Department of Internal Medicine, Leiden University Medical Center, Albinusdreef 2, C7-36, PO Box 9600, 2300RC Leiden, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hetty C.","family":"de Boer","sequence":"additional","affiliation":[{"name":"Einthoven Laboratory for Experimental Vascular Medicine, Division of Nephrology, Department of Internal Medicine, Leiden University Medical Center, Albinusdreef 2, C7-36, PO Box 9600, 2300RC Leiden, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ton J.","family":"Rabelink","sequence":"additional","affiliation":[{"name":"Einthoven Laboratory for Experimental Vascular Medicine, Division of Nephrology, Department of Internal Medicine, Leiden University Medical Center, Albinusdreef 2, C7-36, PO Box 9600, 2300RC Leiden, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1676-7738","authenticated-orcid":false,"given":"Anton Jan","family":"van Zonneveld","sequence":"additional","affiliation":[{"name":"Einthoven Laboratory for Experimental Vascular Medicine, Division of Nephrology, Department of Internal Medicine, Leiden University Medical Center, Albinusdreef 2, C7-36, PO Box 9600, 2300RC Leiden, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eric P.","family":"van der Veer","sequence":"additional","affiliation":[{"name":"Einthoven Laboratory for Experimental Vascular Medicine, Division of Nephrology, Department of Internal Medicine, Leiden University Medical Center, Albinusdreef 2, C7-36, PO Box 9600, 2300RC Leiden, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"St\u00e9phane","family":"Richard","sequence":"additional","affiliation":[{"name":"Segal Cancer Center, Lady Davis Institute for Medical Research and Gerald Bronfman Department of Oncology and Departments of Biochemistry, Human Genetics and Medicine, McGill University, Montr\u00e9al, QC H3T 1E2, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,2,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"R91","DOI":"10.1530\/ERC-11-0041","article-title":"The RNA-binding protein sam68 is a multifunctional player in human cancer","volume":"18","author":"Bielli","year":"2011","journal-title":"Endocr. 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