{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,2]],"date-time":"2026-11-02T22:13:01Z","timestamp":1793657581226,"version":"4.5.1"},"reference-count":37,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,6,4]],"date-time":"2021-06-04T00:00:00Z","timestamp":1622764800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,6,4]],"date-time":"2021-06-04T00:00:00Z","timestamp":1622764800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Foundation Tysta Skolan"},{"name":"Uppsala University Hospital ALF Grants"},{"name":"Foundation Acta Otolaryngologica"},{"DOI":"10.13039\/501100001862","name":"the Swedish Research Council","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100001862","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The endolymphatic sac (ES) is the third part of the inner ear, along with the cochlea and vestibular apparatus. A refined sampling technique was developed to analyse the proteomics of ES endolymph. With a tailored solid phase micro-extraction probe, five ES endolymph samples were collected, and six sac tissue biopsies were obtained in patients undergoing trans-labyrinthine surgery for sporadic vestibular schwannoma. The samples were analysed using nano-liquid chromatography-tandem mass spectrometry (nLC-MS\/MS) to identify the total number of proteins. Pathway identification regarding molecular function and protein class was presented. A total of 1656 non-redundant proteins were identified, with 1211 proteins detected in the ES endolymph. A total of 110 proteins were unique to the ES endolymph. The results from the study both validate a strategy for in vivo and in situ human sampling during surgery and may also form a platform for further investigations to better understand the function of this intriguing part of the inner ear.<\/jats:p>","DOI":"10.1038\/s41598-021-89597-3","type":"journal-article","created":{"date-parts":[[2021,6,4]],"date-time":"2021-06-04T06:04:47Z","timestamp":1622786687000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["The proteome of the human endolymphatic sac endolymph"],"prefix":"10.1038","volume":"11","author":[{"given":"Christine","family":"\u00d6lander","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jesper","family":"Edvardsson Rasmussen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Per Olof","family":"Eriksson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G\u00f6ran","family":"Laurell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helge","family":"Rask-Andersen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonas","family":"Bergquist","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,6,4]]},"reference":[{"key":"89597_CR1","doi-asserted-by":"publisher","first-page":"1813","DOI":"10.1007\/s00405-016-4362-1","volume":"274","author":"N Mori","year":"2017","unstructured":"Mori, N. et al. Ion transport its regulation in the endolymphatic sac: Suggestions for clinical aspects of Meniere\u2019s disease. Eur. Arch. Otorhinolaryngol. 274, 1813\u20131820. https:\/\/doi.org\/10.1007\/s00405-016-4362-1 (2017).","journal-title":"Eur. Arch. Otorhinolaryngol."},{"key":"89597_CR2","doi-asserted-by":"publisher","first-page":"e21656","DOI":"10.1371\/journal.pone.0021656","volume":"6","author":"SH Kim","year":"2011","unstructured":"Kim, S. H. et al. Albumin-like protein is the major protein constituent of luminal fluid in the human endolymphatic sac. PLoS ONE 6, e21656. https:\/\/doi.org\/10.1371\/journal.pone.0021656 (2011).","journal-title":"PLoS ONE"},{"key":"89597_CR3","doi-asserted-by":"publisher","first-page":"306","DOI":"10.1111\/j.1749-6632.2001.tb03755.x","volume":"942","author":"AN Salt","year":"2001","unstructured":"Salt, A. N. Regulation of endolymphatic fluid volume. Ann. N. Y. Acad. Sci. 942, 306\u2013312. https:\/\/doi.org\/10.1111\/j.1749-6632.2001.tb03755.x (2001).","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"89597_CR4","doi-asserted-by":"publisher","first-page":"283","DOI":"10.3109\/00016488009127140","volume":"89","author":"H Rask-Andersen","year":"1980","unstructured":"Rask-Andersen, H. & Stahle, J. Immunodefence of the inner ear? Lymphocyte-macrophage interaction in the endolymphatic sac. Acta Otolaryngol. 89, 283\u2013294. https:\/\/doi.org\/10.3109\/00016488009127140 (1980).","journal-title":"Acta Otolaryngol."},{"key":"89597_CR5","doi-asserted-by":"publisher","first-page":"3181","DOI":"10.3389\/fimmu.2018.03181","volume":"9","author":"C Kampfe Nordstrom","year":"2018","unstructured":"Kampfe Nordstrom, C., Danckwardt-Lilliestrom, N., Laurell, G., Liu, W. & Rask-Andersen, H. The human endolymphatic sac and inner ear immunity: Macrophage interaction and molecular expression. Front. Immunol. 9, 3181. https:\/\/doi.org\/10.3389\/fimmu.2018.03181 (2018).","journal-title":"Front. Immunol."},{"key":"89597_CR6","doi-asserted-by":"publisher","first-page":"E201","DOI":"10.1002\/lary.26074","volume":"127","author":"MN Moller","year":"2017","unstructured":"Moller, M. N., Kirkeby, S., Vikesa, J., Nielsen, F. C. & Caye-Thomasen, P. The human endolymphatic sac expresses natriuretic peptides. Laryngoscope 127, E201\u2013E208. https:\/\/doi.org\/10.1002\/lary.26074 (2017).","journal-title":"Laryngoscope"},{"key":"89597_CR7","doi-asserted-by":"publisher","first-page":"113","DOI":"10.1177\/000348940111000204","volume":"110","author":"RA Buckingham","year":"2001","unstructured":"Buckingham, R. A. & Valvassori, G. E. Inner ear fluid volumes and the resolving power of magnetic resonance imaging: Can it differentiate endolymphatic structures? Ann. Otol. Rhinol. Laryngol. 110, 113\u2013117. https:\/\/doi.org\/10.1177\/000348940111000204 (2001).","journal-title":"Ann. Otol. Rhinol. Laryngol."},{"key":"89597_CR8","unstructured":"Pawliszyn, J. Handbook of SPME (Chemical Industry Press, Beijing, 2009)."},{"key":"89597_CR9","doi-asserted-by":"publisher","first-page":"2057","DOI":"10.1007\/s00216-011-5614-y","volume":"402","author":"AP Dahlin","year":"2012","unstructured":"Dahlin, A. P. et al. Multiplexed quantification of proteins adsorbed to surface-modified and non-modified microdialysis membranes. Anal. Bioanal. Chem. 402, 2057\u20132067. https:\/\/doi.org\/10.1007\/s00216-011-5614-y (2012).","journal-title":"Anal. Bioanal. Chem."},{"key":"89597_CR10","doi-asserted-by":"publisher","first-page":"1551","DOI":"10.1038\/nprot.2013.092","volume":"8","author":"H Mi","year":"2013","unstructured":"Mi, H., Muruganujan, A., Casagrande, J. T. & Thomas, P. D. Large-scale gene function analysis with the PANTHER classification system. Nat. Protoc. 8, 1551\u20131566. https:\/\/doi.org\/10.1038\/nprot.2013.092 (2013).","journal-title":"Nat. Protoc."},{"key":"89597_CR11","doi-asserted-by":"publisher","first-page":"1911","DOI":"10.1021\/acs.jproteome.6b00986","volume":"16","author":"HA Schmitt","year":"2017","unstructured":"Schmitt, H. A. et al. Proteome analysis of human perilymph using an intraoperative sampling method. J. Proteome Res. 16, 1911\u20131923. https:\/\/doi.org\/10.1021\/acs.jproteome.6b00986 (2017).","journal-title":"J. Proteome Res."},{"key":"89597_CR12","doi-asserted-by":"publisher","first-page":"e0198442","DOI":"10.1371\/journal.pone.0198442","volume":"13","author":"J Edvardsson Rasmussen","year":"2018","unstructured":"Edvardsson Rasmussen, J., Laurell, G., Rask-Andersen, H., Bergquist, J. & Eriksson, P. O. The proteome of perilymph in patients with vestibular schwannoma. A possibility to identify biomarkers for tumor associated hearing loss? PLoS ONE 13, e0198442. https:\/\/doi.org\/10.1371\/journal.pone.0198442 (2018).","journal-title":"PLoS ONE"},{"key":"89597_CR13","first-page":"134","volume":"7","author":"D Bagger-Sj\u00f6b\u00e4ck","year":"1986","unstructured":"Bagger-Sj\u00f6b\u00e4ck, D. & Rask-Andersen, H. The permeability barrier of the endolymphatic sac. A hypothesis of fluid and electrolyte exchange based on freeze fracturing. Am. J. Otol. 7, 134\u2013140 (1986).","journal-title":"Am. J. Otol."},{"key":"89597_CR14","doi-asserted-by":"publisher","first-page":"3845","DOI":"10.1021\/pr200346q","volume":"10","author":"AC Lysaght","year":"2011","unstructured":"Lysaght, A. C. et al. Proteome of human perilymph. J. Proteome Res. 10, 3845\u20133851. https:\/\/doi.org\/10.1021\/pr200346q (2011).","journal-title":"J. Proteome Res."},{"key":"89597_CR15","doi-asserted-by":"publisher","first-page":"9340","DOI":"10.1038\/s41598-019-45646-6","volume":"9","author":"M Sole","year":"2019","unstructured":"Sole, M., Monge, M., Andre, M. & Quero, C. A proteomic analysis of the statocyst endolymph in common cuttlefish (Sepia officinalis): An assessment of acoustic trauma after exposure to sound. Sci. Rep. 9, 9340. https:\/\/doi.org\/10.1038\/s41598-019-45646-6 (2019).","journal-title":"Sci. Rep."},{"key":"89597_CR16","first-page":"293","volume":"14","author":"I Teichmann","year":"1964","unstructured":"Teichmann, I., Vigh, B. & Aros, B. Histochemical studies on gomori-positive substances. I. Examination of the gomori-positive substance in the endolymphatic sac of the rat. Acta Biol. Acad. Sci. Hung. 14, 293\u2013300 (1964).","journal-title":"Acta Biol. Acad. Sci. Hung."},{"key":"89597_CR17","doi-asserted-by":"publisher","first-page":"63","DOI":"10.3109\/00016488909127480","volume":"107","author":"C Erwall","year":"1989","unstructured":"Erwall, C., Takumida, M., Bagger-Sjoback, D., Rask-Andersen, H. & Wroblewski, J. Uptake of radioactive sulphur in the endolymphatic sac. An autoradiographic study. Acta Otolaryngol. 107, 63\u201370. https:\/\/doi.org\/10.3109\/00016488909127480 (1989).","journal-title":"Acta Otolaryngol."},{"key":"89597_CR18","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/0167-0115(95)00015-4","volume":"57","author":"C Sernia","year":"1995","unstructured":"Sernia, C. Location and secretion of brain angiotensinogen. Regul. Pept. 57, 1\u201318. https:\/\/doi.org\/10.1016\/0167-0115(95)00015-4 (1995).","journal-title":"Regul. Pept."},{"key":"89597_CR19","doi-asserted-by":"publisher","first-page":"126","DOI":"10.1007\/bf02555696","volume":"40","author":"DI Hay","year":"1987","unstructured":"Hay, D. I., Carlson, E. R., Schluckebier, S. K., Moreno, E. C. & Schlesinger, D. H. Inhibition of calcium phosphate precipitation by human salivary acidic proline-rich proteins: Structure-activity relationships. Calcif. Tissue Int. 40, 126\u2013132. https:\/\/doi.org\/10.1007\/bf02555696 (1987).","journal-title":"Calcif. Tissue Int."},{"key":"89597_CR20","doi-asserted-by":"publisher","first-page":"2225","DOI":"10.1101\/gad.267708.115","volume":"29","author":"BK Sun","year":"2015","unstructured":"Sun, B. K. et al. CALML5 is a ZNF750- and TINCR-induced protein that binds stratifin to regulate epidermal differentiation. Genes Dev. 29, 2225\u20132230. https:\/\/doi.org\/10.1101\/gad.267708.115 (2015).","journal-title":"Genes Dev."},{"key":"89597_CR21","doi-asserted-by":"publisher","first-page":"2861","DOI":"10.3892\/mmr.2017.8194","volume":"17","author":"YH Liu","year":"2018","unstructured":"Liu, Y. H. et al. Electrophysiological properties of strial pericytes and the effect of aspirin on pericyte K+ channels. Mol. Med. Rep. 17, 2861\u20132868. https:\/\/doi.org\/10.3892\/mmr.2017.8194 (2018).","journal-title":"Mol. Med. Rep."},{"key":"89597_CR22","doi-asserted-by":"publisher","first-page":"e10980","DOI":"10.1371\/journal.pone.0010980","volume":"5","author":"SE Schutzer","year":"2010","unstructured":"Schutzer, S. E. et al. Establishing the proteome of normal human cerebrospinal fluid. PLoS ONE 5, e10980. https:\/\/doi.org\/10.1371\/journal.pone.0010980 (2010).","journal-title":"PLoS ONE"},{"key":"89597_CR23","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1258\/000456303321016141","volume":"40","author":"MM Verbeek","year":"2003","unstructured":"Verbeek, M. M., De Jong, D. & Kremer, H. P. Brain-specific proteins in cerebrospinal fluid for the diagnosis of neurodegenerative diseases. Ann. Clin. Biochem. 40, 25\u201340. https:\/\/doi.org\/10.1258\/000456303321016141 (2003).","journal-title":"Ann. Clin. Biochem."},{"key":"89597_CR24","doi-asserted-by":"publisher","first-page":"1598","DOI":"10.1002\/elps.200500768","volume":"27","author":"I Thalmann","year":"2006","unstructured":"Thalmann, I., Hughes, I., Tong, B. D., Ornitz, D. M. & Thalmann, R. Microscale analysis of proteins in inner ear tissues and fluids with emphasis on endolymphatic sac, otoconia, and organ of Corti. Electrophoresis 27, 1598\u20131608. https:\/\/doi.org\/10.1002\/elps.200500768 (2006).","journal-title":"Electrophoresis"},{"key":"89597_CR25","doi-asserted-by":"publisher","first-page":"1083","DOI":"10.1152\/physrev.1988.68.4.1083","volume":"68","author":"O Sterkers","year":"1988","unstructured":"Sterkers, O., Ferrary, E. & Amiel, C. Production of inner ear fluids. Physiol. Rev. 68, 1083\u20131128. https:\/\/doi.org\/10.1152\/physrev.1988.68.4.1083 (1988).","journal-title":"Physiol. Rev."},{"key":"89597_CR26","doi-asserted-by":"publisher","first-page":"200","DOI":"10.1080\/00016489950181666","volume":"119","author":"V Couloigner","year":"1999","unstructured":"Couloigner, V., Teixeira, M., Sterkers, O. & Ferrary, E. In vivo study of the electrochemical composition of luminal fluid in the guinea pig endolymphatic sac. Acta Otolaryngol. 119, 200\u2013202. https:\/\/doi.org\/10.1080\/00016489950181666 (1999).","journal-title":"Acta Otolaryngol."},{"key":"89597_CR27","doi-asserted-by":"publisher","first-page":"198","DOI":"10.1159\/000276298","volume":"54","author":"S Tsujikawa","year":"1992","unstructured":"Tsujikawa, S., Yamashita, T., Amano, H., Kumazawa, T. & Vosteen, K. H. Acidity in the endolymphatic sac fluid of guinea pigs. J. Otorhinolaryngol. Relat. Spec. 54, 198\u2013200. https:\/\/doi.org\/10.1159\/000276298 (1992).","journal-title":"J. Otorhinolaryngol. Relat. Spec."},{"key":"89597_CR28","doi-asserted-by":"publisher","first-page":"445","DOI":"10.1007\/s00441-019-03106-7","volume":"379","author":"CK Nordstrom","year":"2020","unstructured":"Nordstrom, C. K., Danckwardt-Lilliestrom, N., Liu, W. & Rask-Andersen, H. \u201cReversed polarization\u201d of Na\/K-ATPase-a sign of inverted transport in the human endolymphatic sac: A super-resolution structured illumination microscopy (SR-SIM) study. Cell Tissue Res. 379, 445\u2013457. https:\/\/doi.org\/10.1007\/s00441-019-03106-7 (2020).","journal-title":"Cell Tissue Res."},{"key":"89597_CR29","doi-asserted-by":"publisher","first-page":"343","DOI":"10.1007\/s00401-018-1927-7","volume":"137","author":"AH Eckhard","year":"2019","unstructured":"Eckhard, A. H. et al. Inner ear pathologies impair sodium-regulated ion transport in Meniere\u2019s disease. Acta Neuropathol. 137, 343\u2013357. https:\/\/doi.org\/10.1007\/s00401-018-1927-7 (2019).","journal-title":"Acta Neuropathol."},{"key":"89597_CR30","doi-asserted-by":"publisher","first-page":"685","DOI":"10.1288\/00005537-198606000-00018","volume":"96","author":"S Tomiyama","year":"1986","unstructured":"Tomiyama, S. & Harris, J. P. The endolymphatic sac: Its importance in inner ear immune responses. Laryngoscope 96, 685\u2013691. https:\/\/doi.org\/10.1288\/00005537-198606000-00018 (1986).","journal-title":"Laryngoscope"},{"key":"89597_CR31","doi-asserted-by":"publisher","first-page":"145","DOI":"10.1097\/mao.0000000000002466","volume":"41","author":"E Mulry","year":"2020","unstructured":"Mulry, E. & Parham, K. Inner ear proteins as potential biomarkers. Otol. Neurotol. 41, 145\u2013152. https:\/\/doi.org\/10.1097\/mao.0000000000002466 (2020).","journal-title":"Otol. Neurotol."},{"key":"89597_CR32","doi-asserted-by":"publisher","first-page":"265","DOI":"10.1016\/0378-5955(89)90150-0","volume":"42","author":"A Hara","year":"1989","unstructured":"Hara, A., Salt, A. N. & Thalmann, R. Perilymph composition in scala tympani of the cochlea: Influence of cerebrospinal fluid. Hear Res. 42, 265\u2013271. https:\/\/doi.org\/10.1016\/0378-5955(89)90150-0 (1989).","journal-title":"Hear Res."},{"key":"89597_CR33","doi-asserted-by":"publisher","first-page":"363","DOI":"10.1016\/j.amjoto.2005.02.013","volume":"26","author":"S Berrettini","year":"2005","unstructured":"Berrettini, S. et al. Large vestibular aqueduct syndrome: Audiological, radiological, clinical, and genetic features. Am. J. Otolaryngol. 26, 363\u2013371. https:\/\/doi.org\/10.1016\/j.amjoto.2005.02.013 (2005).","journal-title":"Am. J. Otolaryngol."},{"key":"89597_CR34","doi-asserted-by":"publisher","first-page":"265","DOI":"10.1016\/S0021-9258(19)52451-6","volume":"193","author":"OH Lowry","year":"1951","unstructured":"Lowry, O. H., Rosebrough, N. J., Farr, A. L. & Randall, R. J. Protein measurement with the Folin phenol reagent. J. Biol. Chem. 193, 265\u2013275 (1951).","journal-title":"J. Biol. Chem."},{"key":"89597_CR35","doi-asserted-by":"publisher","first-page":"698","DOI":"10.1038\/nprot.2009.36","volume":"4","author":"J Cox","year":"2009","unstructured":"Cox, J. et al. A practical guide to the MaxQuant computational platform for SILAC-based quantitative proteomics. Nat. Protoc. 4, 698\u2013705. https:\/\/doi.org\/10.1038\/nprot.2009.36 (2009).","journal-title":"Nat. Protoc."},{"key":"89597_CR36","doi-asserted-by":"publisher","first-page":"D158","DOI":"10.1093\/nar\/gkw1099","volume":"45","author":"R Apweiler","year":"2017","unstructured":"Apweiler, R. et al. UniProt: The universal protein knowledgebase. Nucleic Acids Res. 45, D158\u2013D169. https:\/\/doi.org\/10.1093\/nar\/gkw1099 (2017).","journal-title":"Nucleic Acids Res."},{"key":"89597_CR37","doi-asserted-by":"publisher","first-page":"703","DOI":"10.1038\/s41596-019-0128-8","volume":"14","author":"H Mi","year":"2019","unstructured":"Mi, H. et al. Protocol update for large-scale genome and gene function analysis with the PANTHER classification system (v.14.0). Nat. Protoc. 14, 703\u2013721. https:\/\/doi.org\/10.1038\/s41596-019-0128-8 (2019).","journal-title":"Nat. Protoc."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-89597-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-89597-3","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-89597-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,3]],"date-time":"2022-12-03T04:26:28Z","timestamp":1670041588000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-89597-3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,6,4]]},"references-count":37,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2021,12]]}},"alternative-id":["89597"],"URL":"https:\/\/doi.org\/10.1038\/s41598-021-89597-3","relation":{"has-review":[{"id-type":"doi","id":"10.32388\/8TAMXS","asserted-by":"object"}]},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,6,4]]},"assertion":[{"value":"9 December 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"19 April 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"4 June 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"7 November 2021","order":4,"name":"change_date","label":"Change Date","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Update","order":5,"name":"change_type","label":"Change Type","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The original online version of this Article was revised: In the original version of this Article the Funding section was omitted. The correct Funding section now reads: \u201cOpen access funding provided by Uppsala University\u201d.","order":6,"name":"change_details","label":"Change Details","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"11850"}}