{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T19:09:02Z","timestamp":1785179342184,"version":"3.55.0"},"reference-count":43,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2022,5,21]],"date-time":"2022-05-21T00:00:00Z","timestamp":1653091200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Deutsche Forschungsgemeinschaft","award":["PA738\/15-1"],"award-info":[{"award-number":["PA738\/15-1"]}]},{"name":"Deutsche Forschungsgemeinschaft","award":["1\/15"],"award-info":[{"award-number":["1\/15"]}]},{"name":"Deutsche Forschungsgemeinschaft","award":["21-19854S"],"award-info":[{"award-number":["21-19854S"]}]},{"name":"Sicca Forschungsf\u00f6rderung of the professional Association of German Ophthalmologists","award":["PA738\/15-1"],"award-info":[{"award-number":["PA738\/15-1"]}]},{"name":"Sicca Forschungsf\u00f6rderung of the professional Association of German Ophthalmologists","award":["1\/15"],"award-info":[{"award-number":["1\/15"]}]},{"name":"Sicca Forschungsf\u00f6rderung of the professional Association of German Ophthalmologists","award":["21-19854S"],"award-info":[{"award-number":["21-19854S"]}]},{"name":"Ernst und Berta Grimmke Stiftung","award":["PA738\/15-1"],"award-info":[{"award-number":["PA738\/15-1"]}]},{"name":"Ernst und Berta Grimmke Stiftung","award":["1\/15"],"award-info":[{"award-number":["1\/15"]}]},{"name":"Ernst und Berta Grimmke Stiftung","award":["21-19854S"],"award-info":[{"award-number":["21-19854S"]}]},{"name":"Czech Science Fundation","award":["PA738\/15-1"],"award-info":[{"award-number":["PA738\/15-1"]}]},{"name":"Czech Science Fundation","award":["1\/15"],"award-info":[{"award-number":["1\/15"]}]},{"name":"Czech Science Fundation","award":["21-19854S"],"award-info":[{"award-number":["21-19854S"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The ocular surface is in constant interaction with the environment and with numerous pathogens. Therefore, complex mechanisms such as a stable tear film and local immune defense mechanisms are required to protect the eye. This study describes the detection, characterization, and putative role of surfactant protein G (SP-G\/SFTA2) with respect to wound healing and surface activity. Bioinformatic, biochemical, and immunological methods were combined to elucidate the role of SP-G in tear film. The results show the presence of SP-G in ocular surface tissues and tear film (TF). Increased expression of SP-G was demonstrated in TF of patients with dry eye disease (DED). Addition of recombinant SP-G in combination with lipids led to an accelerated wound healing of human corneal cells as well as to a reduction of TF surface tension. Molecular modeling of TF suggest that SP-G may regulate tear film surface tension and improve its stability through specific interactions with lipids components of the tear film. In conclusion, SP-G is an ocular surface protein with putative wound healing properties that can also reduce the surface tension of the tear film.<\/jats:p>","DOI":"10.3390\/ijms23105783","type":"journal-article","created":{"date-parts":[[2022,5,21]],"date-time":"2022-05-21T09:18:08Z","timestamp":1653124688000},"page":"5783","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["The Potential Role of SP-G as Surface Tension Regulator in Tear Film: From Molecular Simulations to Experimental Observations"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5155-5477","authenticated-orcid":false,"given":"Martin","family":"Schicht","sequence":"first","affiliation":[{"name":"Institute of Functional and Clinical Anatomy, Friedrich-Alexander-Universit\u00e4t Erlangen- Nuremberg, Universit\u00e4tsstr. 19, 91054 Erlangen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9134-2297","authenticated-orcid":false,"given":"Kamila","family":"Riedlov\u00e1","sequence":"additional","affiliation":[{"name":"J. Heyrovsk\u00fd Institute of Physical Chemistry, Czech Academy of Sciences, 182 00 Prague, Czech Republic"},{"name":"Department of Physical and Macromolecular Chemistry, Faculty of Science, Charles University, 128 40 Prague, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0918-6097","authenticated-orcid":false,"given":"Mercedes","family":"Kukulka","sequence":"additional","affiliation":[{"name":"J. Heyrovsk\u00fd Institute of Physical Chemistry, Czech Academy of Sciences, 182 00 Prague, Czech Republic"},{"name":"Faculty of Chemistry, Jagiellonian University, 30387 Krakow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenyue","family":"Li","sequence":"additional","affiliation":[{"name":"Institute of Functional and Clinical Anatomy, Friedrich-Alexander-Universit\u00e4t Erlangen- Nuremberg, Universit\u00e4tsstr. 19, 91054 Erlangen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aurelius","family":"Scheer","sequence":"additional","affiliation":[{"name":"Institute of Functional and Clinical Anatomy, Friedrich-Alexander-Universit\u00e4t Erlangen- Nuremberg, Universit\u00e4tsstr. 19, 91054 Erlangen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabian","family":"Garreis","sequence":"additional","affiliation":[{"name":"Institute of Functional and Clinical Anatomy, Friedrich-Alexander-Universit\u00e4t Erlangen- Nuremberg, Universit\u00e4tsstr. 19, 91054 Erlangen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christina","family":"Jacobi","sequence":"additional","affiliation":[{"name":"Ophthalmology Private Practice, 17, 81034 Nuremberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0527-0953","authenticated-orcid":false,"given":"Friedrich","family":"Paulsen","sequence":"additional","affiliation":[{"name":"Institute of Functional and Clinical Anatomy, Friedrich-Alexander-Universit\u00e4t Erlangen- Nuremberg, Universit\u00e4tsstr. 19, 91054 Erlangen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2083-8738","authenticated-orcid":false,"given":"Lukasz","family":"Cwiklik","sequence":"additional","affiliation":[{"name":"J. Heyrovsk\u00fd Institute of Physical Chemistry, Czech Academy of Sciences, 182 00 Prague, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lars","family":"Br\u00e4uer","sequence":"additional","affiliation":[{"name":"Institute of Functional and Clinical Anatomy, Friedrich-Alexander-Universit\u00e4t Erlangen- Nuremberg, Universit\u00e4tsstr. 19, 91054 Erlangen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,5,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"802","DOI":"10.1016\/j.jtos.2017.08.003","article-title":"TFOS DEWS II Report Executive Summary","volume":"15","author":"Craig","year":"2017","journal-title":"Ocul. Surf."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1007\/s40135-013-0009-1","article-title":"Dry Eye Disease: Impact on Quality of Life and Vision","volume":"1","author":"Uchino","year":"2013","journal-title":"Curr. Ophthalmol. Rep."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1090","DOI":"10.1016\/j.bbalip.2011.08.011","article-title":"Identification and characterization of ABCB1-mediated and non-apoptotic sebum secretion in differentiated hamster sebocytes","volume":"1811","author":"Kurihara","year":"2011","journal-title":"Biochim. Et Biophys. Acta"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1016\/j.jtos.2017.05.008","article-title":"TFOS DEWS II Definition and Classification Report","volume":"15","author":"Craig","year":"2017","journal-title":"Ocul. Surf."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1016\/j.oftal.2014.05.001","article-title":"What drives Meibomian gland disease?","volume":"89","author":"Paulsen","year":"2014","journal-title":"Arch. Soc. Esp. Oftalmol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1930","DOI":"10.1167\/iovs.10-6997b","article-title":"The international workshop on meibomian gland dysfunction: Report of the definition and classification subcommittee","volume":"52","author":"Nelson","year":"2011","journal-title":"Investig. Ophthalmol. Vis. Sci"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"803","DOI":"10.1080\/09273948.2021.1905856","article-title":"Pathophysiology of Meibomian Glands\u2014An Overview","volume":"29","author":"Dietrich","year":"2021","journal-title":"Ocul. Immunol. Inflamm."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1979","DOI":"10.1167\/iovs.10-6997d","article-title":"The international workshop on meibomian gland dysfunction: Report of the subcommittee on tear film lipids and lipid-protein interactions in health and disease","volume":"52","author":"Butovich","year":"2011","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/0039-6257(77)90087-X","article-title":"Tear physiology and dry eyes","volume":"22","author":"Holly","year":"1977","journal-title":"Surv. Ophthalmol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1038\/nri1528","article-title":"Immunoregulatory functions of surfactant proteins","volume":"5","author":"Wright","year":"2005","journal-title":"Nat. Rev. Immunol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1146\/annurev.physiol.63.1.521","article-title":"Surfactant proteins a and d and pulmonary host defense","volume":"63","author":"Crouch","year":"2001","journal-title":"Annu. Rev. Physiol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1016\/0005-2760(90)90236-Q","article-title":"Role of bovine pulmonary surfactant-associated proteins in the surface-active property of phospholipid mixtures","volume":"1046","author":"Yu","year":"1990","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Rausch, F., Schicht, M., Paulsen, F., Ngueya, I., Br\u00e4uer, L., and Brandt, W. (2012). \u201cSP-G\u201d, a putative new surfactant protein-tissue localization and 3D structure. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0047789"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1183\/09031936.00179813","article-title":"SFTA3, a novel protein of the lung: Three-dimensional structure, characterisation and immune activation","volume":"44","author":"Schicht","year":"2014","journal-title":"Eur. Respir. J."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"3945","DOI":"10.1167\/iovs.07-0201","article-title":"Detection of Surfactant Proteins A and D in Human Tear Fluid and the Human Lacrimal System","volume":"48","author":"Kindler","year":"2007","journal-title":"Investig. Ophthalmol. Vis. Sci"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"931","DOI":"10.1080\/02713680701694369","article-title":"Detection and Localization of the Hydrophobic Surfactant Proteins B and C in Human Tear Fluid and the Human Lacrimal System","volume":"32","author":"Johl","year":"2007","journal-title":"Curr. Eye Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"864","DOI":"10.1055\/s-0029-1245609","article-title":"The ocular surfactant system and its relevance in the dry eye","volume":"227","author":"Schicht","year":"2010","journal-title":"Klin. Mon. Fur Augenheilkd."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"9791","DOI":"10.1038\/s41598-018-28005-9","article-title":"SFTA3\u2014A novel surfactant protein of the ocular surface and its role in corneal wound healing and tear film surface tension","volume":"8","author":"Schicht","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Mittal, R.A., Hammel, M., Schwarz, J., Heschl, K.M., Bretschneider, N., Flemmer, A.W., Herber-Jonat, S., Konigshoff, M., Eickelberg, O., and Holzinger, A. (2012). SFTA2-A Novel Secretory Peptide Highly Expressed in the Lung-Is Modulated by Lipopolysaccharide but Not Hyperoxia. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0040011"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1086\/302786","article-title":"Fine localization of a major disease-susceptibility locus for diffuse panbronchiolitis","volume":"66","author":"Keicho","year":"2000","journal-title":"Am. J. Hum. Genet."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2513","DOI":"10.1007\/s00894-014-2513-0","article-title":"Protein modeling and molecular dynamics simulation of the two novel surfactant proteins SP-G and SP-H","volume":"20","author":"Rausch","year":"2014","journal-title":"J. Mol. Modeling"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/j.clae.2009.12.007","article-title":"Effect of a liposomal spray on the pre-ocular tear film","volume":"33","author":"Craig","year":"2010","journal-title":"Cont. Lens Anterior Eye"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1053\/meta.2002.33184","article-title":"Neuroendocrine aspects of the response to stress","volume":"51","author":"Miller","year":"2002","journal-title":"Metabolism"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2819","DOI":"10.1110\/ps.04682504","article-title":"Signal peptide prediction based on analysis of experimentally verified cleavage sites","volume":"13","author":"Zhang","year":"2004","journal-title":"Protein Sci."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"7312","DOI":"10.1167\/iovs.15-17560","article-title":"Palate Lung Nasal Clone (PLUNC), a Novel Protein of the Tear Film: Three-Dimensional Structure, Immune Activation, and Involvement in Dry Eye Disease (DED)","volume":"56","author":"Schicht","year":"2015","journal-title":"Investig. Ophthalmol. Vis. Sci"},{"key":"ref_26","first-page":"L958","article-title":"Pulmonary surfactant proteins A and D enhance neutrophil uptake of bacteria","volume":"274","author":"Hartshorn","year":"1998","journal-title":"Am. J. Physiol"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Diler, E., Schicht, M., Rabung, A., Tschernig, T., Meier, C., Rausch, F., Garreis, F., Br\u00e4uer, L., and Paulsen, F. (2014). The novel surfactant protein SP-H enhances the phagocytosis efficiency of macrophage-like cell lines U937 and MH-S. Bmc Res. Notes, 7.","DOI":"10.1186\/1756-0500-7-851"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/S1542-0124(12)70081-2","article-title":"The definition and classification of dry eye disease","volume":"5","author":"Lemp","year":"2007","journal-title":"Ocul. Surf."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"444","DOI":"10.1016\/j.exer.2009.12.009","article-title":"Effect of pro-inflammatory mediators on membrane-associated mucins expressed by human ocular surface epithelial cells","volume":"90","author":"Albertsmeyer","year":"2010","journal-title":"Exp. Eye Res."},{"key":"ref_30","first-page":"251","article-title":"Hormonal influences during fetal lung development","volume":"78","author":"Ballard","year":"1980","journal-title":"Ciba Found. Symp"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"9096","DOI":"10.1073\/pnas.85.23.9096","article-title":"Glucocorticoids both stimulate and inhibit production of pulmonary surfactant protein A in fetal human lung","volume":"85","author":"Liley","year":"1988","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"974","DOI":"10.1055\/s-2006-927266","article-title":"Comparative study of treatment of the dry eye syndrome due to disturbances of the tear film lipid layer with lipid-containing tear substitutes","volume":"223","author":"Dausch","year":"2006","journal-title":"Klin. Mon. Fur Augenheilkd."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"101318","DOI":"10.1016\/j.clae.2020.04.003","article-title":"Prospective randomized study to evaluate the efficacy and tolerability of Ectoin(R) containing Eye Spray (EES09) and comparison to the liposomal Eye Spray Tears Again(R) (TA) in the treatment of dry eye disease","volume":"44","author":"Nosch","year":"2021","journal-title":"Cont. Lens Anterior Eye"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1002\/prot.22570","article-title":"Improving physical realism, stereochemistry, and side-chain accuracy in homology modeling: Four approaches that performed well in CASP8","volume":"77","author":"Krieger","year":"2009","journal-title":"Proteins Struct. Funct. Bioinform."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2421","DOI":"10.1016\/j.bbamem.2016.02.020","article-title":"Tear film lipid layer: A molecular level view","volume":"1858","author":"Cwiklik","year":"2016","journal-title":"Biochim. Et Biophys. Acta"},{"key":"ref_36","first-page":"614","article-title":"An SV40-immortalized human corneal epithelial cell line and its characterization","volume":"36","author":"Ohashi","year":"1995","journal-title":"Investig. Ophthalmol. Vis. Sci"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"4263","DOI":"10.1167\/iovs.03-0560","article-title":"Characterization of a spontaneously immortalized cell line (IOBA-NHC) from normal human conjunctiva","volume":"44","author":"Diebold","year":"2003","journal-title":"Investig. Ophthalmol. Vis. Sci"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"24","DOI":"10.2500\/ajra.2013.27.3838","article-title":"Detection of surfactant proteins A, B, C, and D in human nasal mucosa and their regulation in chronic rhinosinusitis with polyps","volume":"27","author":"Schicht","year":"2013","journal-title":"Am. J. Rhinol. Allergy"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Wizert, A., Iskander, D.R., and Cwiklik, L. (2014). Organization of lipids in the tear film: A molecular-level view. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0092461"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"2289","DOI":"10.1016\/j.bbamem.2017.08.015","article-title":"Interaction of lysozyme with a tear film lipid layer model: A molecular dynamics simulation study","volume":"1859","author":"Wizert","year":"2017","journal-title":"Biochim. Biophys. Acta Biomembr."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"6801","DOI":"10.1039\/c3cs60093a","article-title":"Perspective on the Martini model","volume":"42","author":"Marrink","year":"2013","journal-title":"Chem Soc. Rev."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.softx.2015.06.001","article-title":"GROMACS: High performance molecular simulations through multi-level parallelism from laptops to supercomputers","volume":"1\u20132","author":"Abraham","year":"2015","journal-title":"SoftwareX"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/0263-7855(96)00018-5","article-title":"VMD: Visual molecular dynamics","volume":"14","author":"Humphrey","year":"1996","journal-title":"J. Mol. Graph."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/10\/5783\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T23:16:08Z","timestamp":1760138168000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/10\/5783"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,5,21]]},"references-count":43,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2022,5]]}},"alternative-id":["ijms23105783"],"URL":"https:\/\/doi.org\/10.3390\/ijms23105783","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,5,21]]}}}