{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,20]],"date-time":"2026-06-20T00:40:57Z","timestamp":1781916057321,"version":"3.54.5"},"reference-count":76,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2018,11,18]],"date-time":"2018-11-18T00:00:00Z","timestamp":1542499200000},"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>Diabetes mellitus is a widespread metabolic disorder, and long-term hyperglycemia in diabetics leads to diabetic keratopathy. In the present study, we used a shotgun liquid chromatography\/mass spectrometry-based global proteomic approach using the cornea of streptozotocin-induced diabetic (STZ) rats to examine the mechanisms of delayed corneal wound healing in diabetic keratopathy. Applying a label-free quantitation method based on spectral counting, we identified 188 proteins that showed expression changes of &gt;2.0-fold in the cornea of STZ rats. In particular, the level of lumican expression in the cornea of STZ rats was higher than that of the normal rats. In the cornea of the normal rat, the expression level of lumican was elevated during the wound healing process, and it returned to the same expression level as before cornea injury after the wound was healed completely. On the other hand, a high expression level of lumican in the cornea of STZ rats was still maintained even after the wound was healed completely. In addition, adhesion deficiency in corneal basal cells and Bowman\u2019s membrane was observed in the STZ rat. Thus, abnormally overexpressed lumican may lead to adhesion deficiency in the cornea of STZ rats.<\/jats:p>","DOI":"10.3390\/ijms19113635","type":"journal-article","created":{"date-parts":[[2018,11,21]],"date-time":"2018-11-21T11:23:27Z","timestamp":1542799407000},"page":"3635","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["A Proteomic Approach for Understanding the Mechanisms of Delayed Corneal Wound Healing in Diabetic Keratopathy Using Diabetic Model Rat"],"prefix":"10.3390","volume":"19","author":[{"given":"Tetsushi","family":"Yamamoto","sequence":"first","affiliation":[{"name":"Faculty of Pharmacy, Kindai University, Higashi-Osaka 577-8502, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroko","family":"Otake","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy, Kindai University, Higashi-Osaka 577-8502, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noriko","family":"Hiramatsu","sequence":"additional","affiliation":[{"name":"Laboratory of Molecularbiology and Histochemistry, Fujita Health University Institute of Joint Research, 1-98 Dengakugakubo, Kutsukake, Toyoake, Aichi 470-1192, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9659-3204","authenticated-orcid":false,"given":"Naoki","family":"Yamamoto","sequence":"additional","affiliation":[{"name":"Laboratory of Molecularbiology and Histochemistry, Fujita Health University Institute of Joint Research, 1-98 Dengakugakubo, Kutsukake, Toyoake, Aichi 470-1192, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atsushi","family":"Taga","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy, Kindai University, Higashi-Osaka 577-8502, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noriaki","family":"Nagai","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy, Kindai University, Higashi-Osaka 577-8502, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2018,11,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1016\/j.diabres.2009.10.007","article-title":"Global estimates of the prevalence of diabetes for 2010 and 2030","volume":"87","author":"Shaw","year":"2010","journal-title":"Diabetes Res. Clin. Pract."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Expert Committee on the Diagnosis and Classification of Diabetes Mellitus (2003). Report of the expert committee on the diagnosis and classification of diabetes mellitus. Diabetes Care, 26, S5\u2013S20.","DOI":"10.2337\/diacare.26.2007.S5"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1038\/414813a","article-title":"Biochemistry and molecular cell biology of diabetic complications","volume":"414","author":"Brownlee","year":"2001","journal-title":"Nature"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"S75","DOI":"10.1097\/ICO.0b013e31812f6d8e","article-title":"Deviated mechanism of wound healing in diabetic corneas","volume":"26","author":"Chikama","year":"2007","journal-title":"Cornea"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1159\/000265202","article-title":"Corneal epithelial changes in diabetic rats","volume":"14","author":"Friend","year":"1982","journal-title":"Ophthalmic Res."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1001\/archopht.1992.01080160115045","article-title":"Altered epithelial-basement membrane interactions in diabetic corneas","volume":"110","author":"Azar","year":"1992","journal-title":"Arch. Ophth."},{"key":"ref_7","first-page":"443","article-title":"Non-enzymatic glycation in corneas from normal and diabetic donors and its effects on epithelial cell attachment in vitro","volume":"74","author":"McDermott","year":"2003","journal-title":"Optometry"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1006\/exer.1998.0511","article-title":"Extracellular matrix changes in human corneas after radial keratotomy","volume":"67","author":"Ljubimov","year":"1998","journal-title":"Exp. Eye Res."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1016\/S0014-4835(03)00111-8","article-title":"Human diabetic corneas preserve wound healing, basement membrane, integrin and MMP-10 differences from normal corneas in organ culture","volume":"77","author":"Kabosova","year":"2003","journal-title":"Exp. Eye Res."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1141","DOI":"10.2337\/diabetes.55.04.06.db05-1581","article-title":"Insulin treatment ameliorates impaired corneal reepithelialization in diabetic rats","volume":"55","author":"Zagon","year":"2006","journal-title":"Diabetes"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"590","DOI":"10.1167\/iovs.05-1168","article-title":"Delayed wound closure and phenotypic changes in corneal epithelium of the spontaneously diabetic Goto-Kakizaki rat","volume":"48","author":"Wakuta","year":"2007","journal-title":"Invest. Ophth. Vis. Sci."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"418","DOI":"10.1038\/sj.eye.6701497","article-title":"Blinking and superficial punctate keratopathy in patients with diabetes mellitus","volume":"19","author":"Inoue","year":"2005","journal-title":"Eye (Lond)"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"534","DOI":"10.1097\/00003226-200007000-00026","article-title":"Ultrastructural changes in corneas of diabetic patients: An electron-microscopy study","volume":"19","author":"Rehany","year":"2000","journal-title":"Cornea"},{"key":"ref_14","first-page":"142","article-title":"Corneal epithelial fragility in diabetes mellitus","volume":"30","author":"Saini","year":"1995","journal-title":"Can. J. Ophth."},{"key":"ref_15","first-page":"180","article-title":"Diabetic keratopathy","volume":"79","author":"Schultz","year":"1981","journal-title":"Trans. Am. Ophthal. Soc."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1083\/jcb.109.2.571","article-title":"Enhancement of vinculin synthesis by migrating stratified squamous epithelium","volume":"109","author":"Zieske","year":"1989","journal-title":"J. Cell Biol."},{"key":"ref_17","first-page":"1997","article-title":"Differential gene expression in healing rat corneal epithelium","volume":"36","author":"Yu","year":"1995","journal-title":"Invest. Ophth. Vis. Sci."},{"key":"ref_18","first-page":"710","article-title":"Expression and distribution of adhesion molecule CD44 in healing corneal epithelia","volume":"39","author":"Yu","year":"1998","journal-title":"Invest. Ophth. Vis. Sci."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1111\/1523-1747.ep12605917","article-title":"Collagenase expression is rapidly induced in wound-edge keratinocytes after acute injury in human skin, persists during healing, and stops at re-epithelialization","volume":"104","author":"Inoue","year":"1995","journal-title":"J. Invest. Dermatol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2858","DOI":"10.1172\/JCI116906","article-title":"Cell-matrix interactions modulate interstitial collagenase expression by human keratinocytes actively involved in wound healing","volume":"92","author":"Kovacs","year":"1993","journal-title":"J. Clin. Invest."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"3705","DOI":"10.1073\/pnas.77.6.3705","article-title":"Macular corneal dystrophy: Failure to synthesize a mature keratan sulfate proteoglycan","volume":"77","author":"Hassell","year":"1980","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1007\/s003359900757","article-title":"Cloning and chromosomal localization of mouse keratocan, a corneal keratan sulfate proteoglycan","volume":"9","author":"Dunlevy","year":"1998","journal-title":"Mamm. Genome"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1016\/j.exer.2011.01.008","article-title":"Differential epithelial and stromal protein profiles in keratoconus and normal human corneas","volume":"92","author":"Joseph","year":"2011","journal-title":"Exp. Eye Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"818","DOI":"10.1002\/iub.131","article-title":"Lumican, a small leucine-rich proteoglycan","volume":"60","author":"Nikitovic","year":"2008","journal-title":"IUBMB Life"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1146\/annurev.biochem.67.1.609","article-title":"Matrix proteoglycans: From molecular design to cellular function","volume":"67","author":"Iozzo","year":"1998","journal-title":"Annu. Rev. Biochem."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2607","DOI":"10.1074\/jbc.275.4.2607","article-title":"Role of lumican in the corneal epithelium during wound healing","volume":"275","author":"Saika","year":"2000","journal-title":"J. Biol. Chem."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1277","DOI":"10.1083\/jcb.141.5.1277","article-title":"Lumican regulates collagen fibril assembly: Skin fragility and corneal opacity in the absence of lumican","volume":"141","author":"Chakravarti","year":"1998","journal-title":"J. Cell Biol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2030","DOI":"10.1002\/jcp.22932","article-title":"Up-regulation of heat shock protein 70-1 (Hsp70-1) in human limbo-corneal epithelial cells cultivated on amniotic membrane: A proteomic study","volume":"227","author":"Ma","year":"2012","journal-title":"J. Cell. Physiol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1609","DOI":"10.3892\/or.2013.2612","article-title":"Analysis of protein expression regulated by lumican in PANC-1 cells using shotgun proteomics","volume":"30","author":"Yamamoto","year":"2013","journal-title":"Oncol. Rep."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1186\/1477-5956-7-23","article-title":"Enhanced detection method for corneal protein identification using shotgun proteomics","volume":"7","author":"Meade","year":"2009","journal-title":"Proteome Sci."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"445","DOI":"10.3892\/br.2017.988","article-title":"Proteomic profile of the lens in a streptozotocin-induced diabetic rat model using shotgun proteomics","volume":"7","author":"Nagai","year":"2017","journal-title":"Biomed. Rep."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"21942","DOI":"10.1074\/jbc.270.37.21942","article-title":"The human lumican gene. Organization, chromosomal location, and expression in articular cartilage","volume":"270","author":"Grover","year":"1995","journal-title":"J. Biol. Chem."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1006\/geno.1995.1080","article-title":"Primary structure of human lumican (keratan sulfate proteoglycan) and localization of the gene (LUM) to chromosome 12q21.3-q22","volume":"27","author":"Chakravarti","year":"1995","journal-title":"Genomics"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1272\/jnms.72.137","article-title":"Role of the small leucine-rich proteoglycan (SLRP) family in pathological lesions and cancer cell growth","volume":"72","author":"Naito","year":"2005","journal-title":"J. Nippon Med. Sch."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"951","DOI":"10.1093\/glycob\/10.10.951","article-title":"Keratan sulfate: Structure, biosynthesis, and function","volume":"10","author":"Funderburgh","year":"2000","journal-title":"Glycobiology"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1536\/ihj.15-252","article-title":"Aberrant Glycosylation of Lumican in Aortic Valve Stenosis Revealed by Proteomic Analysis","volume":"57","author":"Suzuki","year":"2016","journal-title":"Int. Heart J."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"74466","DOI":"10.18632\/oncotarget.20169","article-title":"The significance of lumican expression in ovarian cancer drug-resistant cell lines","volume":"8","author":"Klejewski","year":"2017","journal-title":"Oncotarget"},{"key":"ref_38","first-page":"1177","article-title":"Expression and roles of lumican in lung adenocarcinoma and squamous cell carcinoma","volume":"33","author":"Matsuda","year":"2008","journal-title":"Int. J. Oncol."},{"key":"ref_39","first-page":"537","article-title":"Role of lumican in cancer cells and adjacent stromal tissues in human pancreatic cancer","volume":"18","author":"Ishiwata","year":"2007","journal-title":"Oncol. Rep."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1641","DOI":"10.1167\/iovs.17-22716","article-title":"Keratan Sulfate Phenotype in the beta-1,3-N-Acetylglucosaminyltransferase-7-Null Mouse Cornea","volume":"59","author":"Littlechild","year":"2018","journal-title":"Invest. Ophth. Vis. Sci."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"933","DOI":"10.1248\/bpb.32.933","article-title":"Enhancing effects of sericin on corneal wound healing in rat debrided corneal epithelium","volume":"32","author":"Nagai","year":"2009","journal-title":"Biol. Pharm. Bull."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1016\/j.jep.2012.07.006","article-title":"Antidiabetic and antioxidant activities of Toddalia asiatica (L.) Lam. leaves in streptozotocin induced diabetic rats","volume":"143","author":"Sunil","year":"2012","journal-title":"J. Ethnopharmacol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1838","DOI":"10.1016\/j.jff.2013.09.003","article-title":"Flavanoid rich ethyl acetate fraction of Musa paradisiaca inflorescence down-regulates the streptozotocin induced oxidative stress, hyperglycaemia and mRNA levels of selected inflammatory genes in rats","volume":"5","author":"Nisha","year":"2013","journal-title":"J. Funct. Foods"},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Nagai, N., Deguchi, S., Otake, H., Hiramatsu, N., and Yamamoto, N. (2017). Therapeutic Effect of Cilostazol Ophthalmic Nanodispersions on Retinal Dysfunction in Streptozotocin-Induced Diabetic Rats. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18091971"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1573","DOI":"10.3892\/ijo.2015.2858","article-title":"Cystatin B as a potential diagnostic biomarker in ovarian clear cell carcinoma","volume":"46","author":"Takaya","year":"2015","journal-title":"Int. J. Oncol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1007","DOI":"10.3892\/ijo.2016.3323","article-title":"Insulin-like growth factor 2 mRNA-binding protein-3 as a marker for distinguishing between cutaneous squamous cell carcinoma and keratoacanthoma","volume":"48","author":"Kanzaki","year":"2016","journal-title":"Int. J. Oncol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"13595","DOI":"10.1007\/s13277-016-5275-8","article-title":"Identification of aldolase A as a potential diagnostic biomarker for colorectal cancer based on proteomic analysis using formalin-fixed paraffin-embedded tissue","volume":"37","author":"Yamamoto","year":"2016","journal-title":"Tumor Biol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"4896","DOI":"10.3892\/ol.2016.5304","article-title":"Increased expression of PDIA3 and its association with cancer cell proliferation and poor prognosis in hepatocellular carcinoma","volume":"12","author":"Takata","year":"2016","journal-title":"Oncol. Lett."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1006\/exer.1993.1081","article-title":"Regulation of Corneal Collagen Fibrillogenesis Invitro by Corneal Proteoglycan (Lumican and Decorin) Core Proteins","volume":"56","author":"Rada","year":"1993","journal-title":"Exp. Eye Res."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1016\/S0014-5793(00)01314-4","article-title":"Fibromodulin and lumican bind to the same region on collagen type I fibrils","volume":"470","author":"Svensson","year":"2000","journal-title":"FEBS Lett."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1023\/A:1025348417078","article-title":"Functions of lumican and fibromodulin: Lessons from knockout mice","volume":"19","author":"Chakravarti","year":"2002","journal-title":"Glycoconj. J."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1042\/bj2230587","article-title":"Specific inhibition of type I and type II collagen fibrillogenesis by the small proteoglycan of tendon","volume":"223","author":"Vogel","year":"1984","journal-title":"Biochem. J."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1068","DOI":"10.1016\/j.actbio.2011.11.012","article-title":"Adhesion, phenotypic expression, and biosynthetic capacity of corneal keratocytes on surfaces coated with hyaluronic acid of different molecular weights","volume":"8","author":"Lai","year":"2012","journal-title":"Acta Biomater."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/j.exer.2014.01.005","article-title":"Corneal stromal stem cells versus corneal fibroblasts in generating structurally appropriate corneal stromal tissue","volume":"120","author":"Wu","year":"2014","journal-title":"Exp. Eye Res."},{"key":"ref_55","first-page":"179","article-title":"Wound Healing in Partial Denudation of Corneal Epithelium of Diabetic Rat","volume":"17","author":"Bendimerad","year":"1987","journal-title":"Kitasato Med."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1167\/iovs.04-0833","article-title":"Lumican regulates corneal inflammatory responses by modulating Fas-Fas ligand signaling","volume":"46","author":"Vij","year":"2005","journal-title":"Invest. Ophth. Vis. Sci."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1007\/s10456-007-9075-z","article-title":"Transcriptome analysis of endothelial cell gene expression induced by growth on matrigel matrices: Identification and characterization of MAGP-2 and lumican as novel regulators of angiogenesis","volume":"10","author":"Albig","year":"2007","journal-title":"Angiogenesis"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"4489","DOI":"10.1074\/jbc.274.8.4489","article-title":"Decorin is a biological ligand for the epidermal growth factor receptor","volume":"274","author":"Iozzo","year":"1999","journal-title":"J. Biol. Chem."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1172\/JCI846","article-title":"Decorin suppresses tumor cell growth by activating the epidermal growth factor receptor","volume":"101","author":"Moscatello","year":"1998","journal-title":"J. Clin. Invest."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1111\/j.1600-0420.2004.00232.x","article-title":"Biglycan gene expression in UVR-exposed rabbit corneas","volume":"82","author":"Podskochy","year":"2004","journal-title":"Acta Ophthalmol. Scan."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1016\/0378-8741(89)90001-9","article-title":"A Review of Natural-Products and Plants as Potential Antidiabetic Drugs","volume":"27","author":"Ivorra","year":"1989","journal-title":"J. Ethnopharmacol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1016\/j.yexmp.2014.06.007","article-title":"Comparative evaluation of torasemide and furosemide on rats with streptozotocin-induced diabetic nephropathy","volume":"97","author":"Arumugam","year":"2014","journal-title":"Exp. Mol. Pathol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1408","DOI":"10.1167\/iovs.15-19026","article-title":"Hyperglycemia Enhances the Production of Amyloid beta1-42 in the Lenses of Otsuka Long-Evans Tokushima Fatty Rats, a Model of Human Type 2 Diabetes","volume":"57","author":"Nagai","year":"2016","journal-title":"Invest. Ophth. Vis. Sci."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"859","DOI":"10.1038\/nprot.2011.333","article-title":"Monitoring protein expression in whole-cell extracts by targeted label- and standard-free LC-MS\/MS","volume":"6","author":"Bluemlein","year":"2011","journal-title":"Nat. Protoc."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1487","DOI":"10.1074\/mcp.M500084-MCP200","article-title":"Comparison of label-free methods for quantifying human proteins by shotgun proteomics","volume":"4","author":"Old","year":"2005","journal-title":"Mol. Cell. Proteom."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"6218","DOI":"10.1021\/ac050846r","article-title":"Correlation of relative abundance ratios derived from peptide ion chromatograms and spectrum counting for quantitative proteomic analysis using stable isotope labeling","volume":"77","author":"Zybailov","year":"2005","journal-title":"Anal. Chem."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"R60","DOI":"10.1186\/gb-2003-4-9-r60","article-title":"DAVID: Database for Annotation, Visualization, and Integrated Discovery","volume":"4","author":"Dennis","year":"2003","journal-title":"Genome Biol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1038\/nprot.2008.211","article-title":"Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources","volume":"4","author":"Sherman","year":"2009","journal-title":"Nat. Protoc."},{"key":"ref_69","first-page":"13.11.1","article-title":"Extracting biological meaning from large gene lists with DAVID","volume":"27","author":"Sherman","year":"2009","journal-title":"Curr. Protoc. Bioinf."},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Nagai, N., Fukuoka, Y., Ishii, M., Otake, H., Yamamoto, T., Taga, A., Okamoto, N., and Shimomura, Y. (2018). Instillation of Sericin Enhances Corneal Wound Healing through the ERK Pathway in Rat Debrided Corneal Epithelium. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19041123"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/j.exer.2016.07.003","article-title":"Size effect of rebamipide ophthalmic nanodispersions on its therapeutic efficacy for corneal wound healing","volume":"151","author":"Nagai","year":"2016","journal-title":"Exp. Eye Res."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1063","DOI":"10.1248\/bpb.b15-00227","article-title":"Hypercalcemia Leads to Delayed Corneal Wound Healing in Ovariectomized Rats","volume":"38","author":"Nagai","year":"2015","journal-title":"Biol. Pharm. Bull."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"743","DOI":"10.5650\/jos.ess14275","article-title":"Decrease in Corneal Damage due to Benzalkonium Chloride by the Addition of Mannitol into Timolol Maleate Eye Drops","volume":"64","author":"Nagai","year":"2015","journal-title":"J. Oleo. Sci."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1023\/A:1023993400608","article-title":"Sericin, a protein derived from silkworms, accelerates the proliferation of several mammalian cell lines including a hybridoma","volume":"40","author":"Terada","year":"2002","journal-title":"Cytotechnology"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1007\/s00795-008-0395-x","article-title":"A study of the proliferating activity in lens epithelium and the identification of tissue-type stem cells","volume":"41","author":"Yamamoto","year":"2008","journal-title":"Med. Mol. Morphol."},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Deguchi, S., Otake, H., Nakazawa, Y., Hiramatsu, N., Yamamoto, N., and Nagai, N. (2017). Ophthalmic Formulation Containing Nilvadipine Nanoparticles Prevents Retinal Dysfunction in Rats Injected with Streptozotocin. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18122720"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/19\/11\/3635\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T15:30:30Z","timestamp":1760196630000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/19\/11\/3635"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,11,18]]},"references-count":76,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2018,11]]}},"alternative-id":["ijms19113635"],"URL":"https:\/\/doi.org\/10.3390\/ijms19113635","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,11,18]]}}}