{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,19]],"date-time":"2026-01-19T13:01:22Z","timestamp":1768827682300,"version":"3.49.0"},"reference-count":56,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2023,11,20]],"date-time":"2023-11-20T00:00:00Z","timestamp":1700438400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Cellular Molecular Medi"],"published-print":{"date-parts":[[2024,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The processes involved in regeneration of cutaneous compared to corneal tissues involve different intrinsic mechanisms. Importantly, cutaneous wounds involve healing by angiogenesis but vascularization of the cornea obscures vision. Previous studies showed that topically applied calreticulin (CALR) healed full\u2010thickness excisional animal wounds by a tissue regenerative process markedly enhancing repair without evoking angiogenesis. In the current study, the application of CALR in a rabbit corneal injury model: (1) accelerated full wound closure by 3\u2009days (2) accelerated delayed healing caused by corticosteroids, routinely used to prevent post\u2010injury inflammation, by 6\u2009days and (3) healed wounds without vascularization or fibrosis\/hazing. In\u00a0vitro, CALR stimulated proliferation of human corneal epithelial cells (CE) and corneal stromal cells (keratocytes) by 1.5\u2010fold and 1.4\u2010fold, respectively and induced migration of CE cells and keratocytes, by 72% and 85% compared to controls of 44% and 59%, respectively. As a marker of decreased fibrosis, CALR treated corneal wounds showed decreased immunostaining for \u03b1\u2010smooth muscle actin (\u03b1\u2010SMA) by keratocytes and following CALR treatment in\u00a0vitro, decreased the levels of TGF\u2010\u03b22 in human CE cells and \u03b1\u2010SMA in keratocytes. CALR has the potential to be a novel therapeutic both, to accelerate corneal healing from various injuries and in conjunction with corticosteroids.<\/jats:p>","DOI":"10.1111\/jcmm.18027","type":"journal-article","created":{"date-parts":[[2023,11,21]],"date-time":"2023-11-21T22:47:44Z","timestamp":1700606864000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Calreticulin accelerates corneal wound closure and mitigates fibrosis: Potential therapeutic applications"],"prefix":"10.1111","volume":"28","author":[{"given":"Sarita","family":"Mishra","sequence":"first","affiliation":[{"name":"Department of Medicine, Division of Precision Medicine New York University School of Medicine Langone Health New York New York USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Miguel A.","family":"Manzanares","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Precision Medicine New York University School of Medicine Langone Health New York New York USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Justin","family":"Prater","sequence":"additional","affiliation":[{"name":"Powered Research, Research Triangle Park North Carolina New York USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"Culp","sequence":"additional","affiliation":[{"name":"Powered Research, Research Triangle Park North Carolina New York USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6925-5392","authenticated-orcid":false,"given":"Leslie I.","family":"Gold","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Precision Medicine New York University School of Medicine Langone Health New York New York USA"},{"name":"Department of Pathology New York University School of Medicine Langone Health New York New York USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2023,11,20]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12192-015-0638-4"},{"issue":"5","key":"e_1_2_9_3_1","first-page":"1083","article-title":"The novel biotherapeutic calreticulin (CRT) corrects multiple defects of non\u2010healing diabetic wounds","volume":"4","author":"Pandya UM","year":"2016","journal-title":"J Derm Clin Res"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1517\/14728222.2016.1164695"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature07039"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.2353\/ajpath.2008.071027"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1524-475X.2012.00822.x"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI32169"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.exer.2020.108089"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms18061257"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biocel.2006.03.010"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcrs.2010.12.037"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.112.5.613"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1350-9462(98)00021-4"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.exer.2020.108002"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.63.1.22"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.13-12106"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.13-12547"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1089\/jop.2017.0021"},{"issue":"8","key":"e_1_2_9_20_1","first-page":"3278","article-title":"Endotoxin\u2010induced uveitis in the rat is attenuated by inhibition of nitric oxide production","volume":"35","author":"Tilton RG","year":"1994","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"e_1_2_9_21_1","doi-asserted-by":"crossref","unstructured":"PandyaUM TellecheaA ManzanaresMA et\u00a0al.Calrreticulin exploits TGF\u2010beta for extracellular matrix induction engineering a tissue regenerative process.2020.","DOI":"10.1096\/fj.202001161R"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40265-021-01660-5"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13346-020-00843-z"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.optom.2014.09.001"},{"issue":"6","key":"e_1_2_9_25_1","doi-asserted-by":"crossref","first-page":"1021","DOI":"10.1242\/jcs.198119","article-title":"Corneal epithelial stem cells and their niche at a glance","volume":"130","author":"Nowell CS","year":"2017","journal-title":"J Cell Sci"},{"issue":"9","key":"e_1_2_9_26_1","first-page":"1789","article-title":"Morphologic analyses of proteoglycans in rabbit corneal scars","volume":"31","author":"Cintron C","year":"1990","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M112.447243"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.2353\/ajpath.2010.090903"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M109.006841"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2022.898772"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1002\/pmic.200700831"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1111\/jcmm.17627"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi500662v"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1080\/07391102.2018.1433065"},{"key":"e_1_2_9_35_1","first-page":"65","article-title":"Corticosteroids in ophthalmology","volume":"40","author":"Pleyer U","year":"2002","journal-title":"Ernst Schering Res Found Workshop"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2012.08.002"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1502122"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2005.08.032"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20020408"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1111\/ceo.14113"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1097\/ICO.0000000000002803"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ophtha.2017.05.012"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.disamonth.2021.101135"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.05-1168"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.survophthal.2020.02.005"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V94.7.2461.419a26_2461_2468"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.1097\/MD.0000000000034210"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms15046019"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10456-017-9591-4"},{"key":"e_1_2_9_50_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-022-04184-7"},{"key":"e_1_2_9_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.actbio.2013.12.002"},{"key":"e_1_2_9_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.actbio.2023.01.016"},{"key":"e_1_2_9_53_1","doi-asserted-by":"publisher","DOI":"10.1089\/jop.2016.0195"},{"key":"e_1_2_9_54_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioadv.2022.213124"},{"key":"e_1_2_9_55_1","doi-asserted-by":"publisher","DOI":"10.2147\/IJN.S195892"},{"key":"e_1_2_9_56_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsami.2c13887"},{"key":"e_1_2_9_57_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.115.4.1091"}],"container-title":["Journal of Cellular and Molecular Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jcmm.18027","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,11,2]],"date-time":"2024-11-02T15:22:38Z","timestamp":1730560958000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/jcmm.18027"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,11,20]]},"references-count":56,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2024,3]]}},"alternative-id":["10.1111\/jcmm.18027"],"URL":"https:\/\/doi.org\/10.1111\/jcmm.18027","archive":["Portico"],"relation":{},"ISSN":["1582-1838","1582-4934"],"issn-type":[{"value":"1582-1838","type":"print"},{"value":"1582-4934","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,11,20]]},"assertion":[{"value":"2023-08-10","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-10-24","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-11-20","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e18027"}}