{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T09:32:39Z","timestamp":1790674359763,"version":"4.1.0"},"reference-count":34,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2022,8,20]],"date-time":"2022-08-20T00:00:00Z","timestamp":1660953600000},"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>Bardet\u2013Biedl syndrome (BBS) is a rare autosomal recessive ciliopathy resulting in multiple organ dysfunctions, including chronic kidney disease (CKD). Despite the recent progress in the \u2019ciliopathy\u2019 field, there is still little information on the mechanisms underlying renal disease. To elucidate these pathomechanisms, we conducted a translational study, including (i) the characterization of the urine metabolomic pattern of BBS patients and controls in a pilot and confirmation study and (ii) the proteomic analysis of the BBS10 interactome, one of the major mutated BBS genes in patients, in a renal-epithelial-derived cell culture model. The urine metabolomic fingerprinting of BBS patients differed from controls in both pilot and confirmation studies, demonstrating an increased urinary excretion of several monocarboxylates, including lactic acid (LA), at both early and late CKD stages. Increased urine LA was detected in the absence of both increased plasmatic LA levels and generalized proximal tubular dysfunction, suggesting a possible renal-specific defective handling. The inner medulla renal epithelial (IMCD3) cell line, where Bbs10 was stably invalidated, displayed an increased proliferative rate, increased ATP production, and an up-regulation of aerobic glycolysis. A mass spectrometry-based analysis detected several putative BBS10 interactors in vitro, indicating a potential role of BBS10 in several biological processes, including renal metabolism, RNA processing, and cell proliferation. The present study suggests that the urine metabolomic pattern of BBS patients may reflect intra-renal metabolic aberrations. The analysis of BBS10 interactors unveils possible novel functions, including cell metabolism.<\/jats:p>","DOI":"10.3390\/ijms23169420","type":"journal-article","created":{"date-parts":[[2022,8,21]],"date-time":"2022-08-21T22:23:13Z","timestamp":1661120593000},"page":"9420","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Multi-Omics Studies Unveil Extraciliary Functions of BBS10 and Show Metabolic Aberrations Underlying Renal Disease in Bardet\u2013Biedl Syndrome"],"prefix":"10.3390","volume":"23","author":[{"given":"Emanuela","family":"Marchese","sequence":"first","affiliation":[{"name":"Department of Mental, Physical Health and Preventive Medicine, University of Campania L.Vanvitelli, 80138 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6035-8213","authenticated-orcid":false,"given":"Marianna","family":"Caterino","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, 80131 Naples, Italy"},{"name":"CEINGE\u2014Biotecnologie Avanzate Franco Salvatore, 80145 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2024-9781","authenticated-orcid":false,"given":"Roberta","family":"Fedele","sequence":"additional","affiliation":[{"name":"CEINGE\u2014Biotecnologie Avanzate Franco Salvatore, 80145 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0150-0202","authenticated-orcid":false,"given":"Francesca","family":"Pirozzi","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1858-2833","authenticated-orcid":false,"given":"Armando","family":"Cevenini","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8181-7378","authenticated-orcid":false,"given":"Neha","family":"Gupta","sequence":"additional","affiliation":[{"name":"Department of Translational Medical Sciences, University of Campania L.Vanvitelli, 80131 Naples, Italy"},{"name":"Biogem S.c.ar.l., 83031 Ariano Irpino, AV, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diego","family":"Ingrosso","sequence":"additional","affiliation":[{"name":"Department of Precision Medicine, University of Campania \u201cLuigi Vanvitelli\u201d, 80138 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4048-9392","authenticated-orcid":false,"given":"Alessandra","family":"Perna","sequence":"additional","affiliation":[{"name":"Department of Translational Medical Sciences, University of Campania L.Vanvitelli, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovambattista","family":"Capasso","sequence":"additional","affiliation":[{"name":"Biogem S.c.ar.l., 83031 Ariano Irpino, AV, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7364-0602","authenticated-orcid":false,"given":"Margherita","family":"Ruoppolo","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, 80131 Naples, Italy"},{"name":"CEINGE\u2014Biotecnologie Avanzate Franco Salvatore, 80145 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0376-2783","authenticated-orcid":false,"given":"Miriam","family":"Zacchia","sequence":"additional","affiliation":[{"name":"Department of Translational Medical Sciences, University of Campania L.Vanvitelli, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,8,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1853","DOI":"10.1093\/ndt\/gfz121","article-title":"Proteomics and metabolomics studies exploring the pathophysiology of renal dysfunction in autosomal dominant polycystic kidney disease and other ciliopathies","volume":"35","author":"Zacchia","year":"2020","journal-title":"Nephrol. 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