{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T14:37:43Z","timestamp":1787495863502,"version":"build-2736575974"},"reference-count":32,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2020,8,20]],"date-time":"2020-08-20T00:00:00Z","timestamp":1597881600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Nephrology"],"published-print":{"date-parts":[[2020,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>Alport syndrome (AS) is the second most common hereditary kidney disease caused by mutations in collagen IV genes. Patients present with microhaematuria that progressively leads to proteinuria and end stage renal disease. Currently, no specific treatment exists for AS. Using mass spectrometry based proteomics, we aimed to detect early alterations in molecular pathways implicated in AS before the stage of overt proteinuria, which could be amenable to therapeutic intervention.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Kidneys were harvested from male\n                      <jats:italic>Col4a3<\/jats:italic>\n                      <jats:sup>\n                        <jats:italic>\u2212\/\u2212<\/jats:italic>\n                      <\/jats:sup>\n                      knock out and sex and age\u2010matched\n                      <jats:italic>Col4a3<\/jats:italic>\n                      <jats:sup>\n                        <jats:italic>+\/+<\/jats:italic>\n                      <\/jats:sup>\n                      wild\u2010type mice at 4\u2009weeks of age. Purified peptides were separated by liquid chromatography and analysed by high resolution mass spectrometry. The Cytoscape bioinformatics tool was used for function enrichment and pathway analysis. PPAR\u03b1 expression levels were evaluated by immunofluorescence and immunoblotting.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Proteomic analysis identified 415 significantly differentially expressed proteins, which were mainly involved in metabolic and cellular processes, the extracellular matrix, binding and catalytic activity. Pathway enrichment analysis revealed among others, downregulation of the proteasome and PPAR pathways. PPAR\u03b1 protein expression levels were observed to be downregulated in Alport mice, supporting further the results of the discovery proteomics.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This study provides additional evidence that alterations in proteins which participate in cellular metabolism and mitochondrial homeostasis in kidney cells are early events in the development of chronic kidney disease in AS. Of note is the dysregulation of the PPAR pathway, which is amenable to therapeutic intervention and provides a new potential target for therapy in AS.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/nep.13764","type":"journal-article","created":{"date-parts":[[2020,8,3]],"date-time":"2020-08-03T02:44:39Z","timestamp":1596422679000},"page":"937-949","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Alport syndrome: Proteomic analysis identifies early molecular pathway alterations in\n                    <i>Col4a3<\/i>\n                    knock out mice"],"prefix":"10.1111","volume":"25","author":[{"given":"Orthodoxia","family":"Nicolaou","sequence":"first","affiliation":[{"name":"Cyprus School of Molecular Medicine The Cyprus Institute of Neurology and Genetics  Nicosia Cyprus"},{"name":"Department of Electron Microscopy and Molecular Pathology The Cyprus Institute of Neurology and Genetics  Nicosia 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