{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T05:15:28Z","timestamp":1789708528494,"version":"4.0.1"},"reference-count":45,"publisher":"Public Library of Science (PLoS)","issue":"7","license":[{"start":{"date-parts":[[2021,7,22]],"date-time":"2021-07-22T00:00:00Z","timestamp":1626912000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"DST-SERB","award":["SB\/FT\/LS-438\/2012"],"award-info":[{"award-number":["SB\/FT\/LS-438\/2012"]}]},{"name":"DST-INSPIRE Program","award":["DST\/INSPIRE\/04\/2017\/002913"],"award-info":[{"award-number":["DST\/INSPIRE\/04\/2017\/002913"]}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\">\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>Diabetic foot ulcer (DFU) is a major concern in diabetes and its control requires in-depth molecular investigation. The present study aimed to screen the expression of microRNA-210 (miR-210) and its association in hypoxic pathway in DFU patients.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>The study consists of 3 groups of circulation samples (50 in each group of: healthy volunteers, T2DM and T2DM with DFU) and 2 groups of tissue samples (10 in each group of: control and T2DM with DFU). Expression of miR-210 and hypoxia inducible factor-1 alpha (HIF-1\u03b1), and its responsive genes such as VEGF, TNF-\u03b1, IL-6, BCl2, Bax and Caspase 3 were analyzed by RT-PCR, Western blot and ELISA analyses.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The HIF-1\u03b1 expression decreased in DFU patients with increased miR-210 expression in both circulation and tissue biopsies. The circulatory IL-6 and inflammatory gene TNF-\u03b1 expression was increased in DFU compared to healthy controls and T2DM subjects. Further, we found there was no alteration in the angiogenic marker, VEGF expression. In comparison, anti-apoptotic BCl2 was decreased and Bax and Caspase 3 was increased in DFU tissues relative to control.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec004\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The study showed that there was an inverse relationship between miR-210 and HIF-1\u03b1 expression in patients with DFU, indicating that miR-210 may regulate the expression of the hypoxic gene.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1371\/journal.pone.0254921","type":"journal-article","created":{"date-parts":[[2021,7,22]],"date-time":"2021-07-22T13:44:59Z","timestamp":1626961499000},"page":"e0254921","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":22,"title":["Impact of microRNA-210 on wound healing among the patients with diabetic foot ulcer"],"prefix":"10.1371","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8018-7877","authenticated-orcid":true,"given":"Sivakamasundari","family":"Pichu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Selvaraj","family":"Vimalraj","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vijay","family":"Viswanathan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2021,7,22]]},"reference":[{"key":"pone.0254921.ref001","doi-asserted-by":"crossref","first-page":"1615","DOI":"10.2337\/diabetes.54.6.1615","article-title":"The pathobiology of diabetic complications: a unifying mechanism","volume":"54","author":"M Brownlee","year":"2005","journal-title":"Diabetes"},{"issue":"suppl 3","key":"pone.0254921.ref002","doi-asserted-by":"crossref","first-page":"S105","DOI":"10.2337\/diab.45.3.S105","article-title":"Biochemical and molecular mechanisms in the development of diabetic vascular complications","volume":"45","author":"GL King","year":"1996","journal-title":"Diabetes"},{"key":"pone.0254921.ref003","doi-asserted-by":"crossref","first-page":"558","DOI":"10.1111\/j.1743-6109.2006.00155.x","article-title":"Chemokines, cytokines, and growth factors in keratinocytes and dermal endothelial cells in the margin of chronic diabetic foot ulcers","volume":"14","author":"H Galkowska","year":"2006","journal-title":"Wound Repair Regen"},{"key":"pone.0254921.ref004","doi-asserted-by":"crossref","first-page":"765","DOI":"10.2353\/ajpath.2006.050293","article-title":"Severely impaired insulin signaling in chronic wounds of diabetic ob\/ob mice: a potential role of tumor necrosis factor-alpha","volume":"168","author":"I Goren","year":"2006","journal-title":"Am. J. Pathol"},{"key":"pone.0254921.ref005","doi-asserted-by":"crossref","first-page":"1736","DOI":"10.1016\/S0140-6736(05)67700-8","article-title":"Wound healing and its impairment in the diabetic foot","volume":"366","author":"V Falanga","year":"2005","journal-title":"Lancet"},{"key":"pone.0254921.ref006","doi-asserted-by":"crossref","first-page":"1178","DOI":"10.2353\/ajpath.2007.060018","article-title":"Decreased macrophage number and activation lead to reduced lymphatic vessel formation and contribute to impaired diabetic would healing","volume":"170","author":"K Maruyama","year":"2007","journal-title":"Am. J. Pathol"},{"key":"pone.0254921.ref007","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1006\/jsre.2002.6525","article-title":"Diminished neuropeptide levels contribute to the impaired cutaneous healing response associated with diabetes mellitus","volume":"108","author":"NS Gibran","year":"2002","journal-title":"J. Surg. Res"},{"key":"pone.0254921.ref008","doi-asserted-by":"crossref","first-page":"1935","DOI":"10.1016\/S0002-9440(10)63754-6","article-title":"Topical vascular endothelial growth factor accelerates diabetic wound healing through increased angiogenesis and by mobilizing and recruiting bone marrow\u2013derived cells","volume":"164","author":"RD Galiano","year":"2004","journal-title":"Am. J. Pathol"},{"issue":"7","key":"pone.0254921.ref009","doi-asserted-by":"crossref","first-page":"1011","DOI":"10.1007\/s00125-002-0868-8","article-title":"Expression of matrixmetalloproteinases and their inhibitors in the wounds of diabetic and non-diabetic patients","volume":"45","author":"R Lobmann","year":"2002","journal-title":"Diabetologia"},{"key":"pone.0254921.ref010","article-title":"Wound fluid lactate concentration: a helpful marker for diagnosing soft-tissue infection in diabetic foot ulcers?","author":"M Loffler","year":"2010","journal-title":"Preliminary findings. Diabetes Medicine"},{"key":"pone.0254921.ref011","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1002\/med.10024","article-title":"Abnormal angiogenesis in diabetes mellitus","volume":"23","author":"A Martin","year":"2003","journal-title":"Med Res Rev"},{"key":"pone.0254921.ref012","doi-asserted-by":"crossref","first-page":"764","DOI":"10.1016\/S0008-6363(96)00091-0","article-title":"Microvasculature in diabetes","volume":"32","author":"JE Tooke","year":"1996","journal-title":"Cardiovasc Res"},{"key":"pone.0254921.ref013","doi-asserted-by":"crossref","first-page":"554","DOI":"10.1016\/S0008-6363(00)00228-5","article-title":"Impaired collateral vessel development in diabetes: potential cellular mechanisms and therapeutic implications","volume":"49","author":"J Waltenberger","year":"2001","journal-title":"Cardiovasc Res"},{"key":"pone.0254921.ref014","doi-asserted-by":"crossref","first-page":"2239","DOI":"10.1161\/01.CIR.99.17.2239","article-title":"Effect of diabetes mellitus on formation of coronary collateral vessels","volume":"99","author":"A Abaci","year":"1999","journal-title":"Circulation"},{"key":"pone.0254921.ref015","doi-asserted-by":"crossref","first-page":"354","DOI":"10.1111\/j.1464-5491.1992.tb01796.x","article-title":"The distribution and severity of diabetic foot disease: a community study with comparison to a non-diabetic group","volume":"9","author":"DP Walters","year":"1992","journal-title":"Diabet Med"},{"key":"pone.0254921.ref016","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1161\/hc0302.102143","article-title":"Decreased cardiac expression of vascular endothelial growth factor and its receptors in insulin-resistant and diabetic States: a possible explanation for impaired collateral formation in cardiac tissue","volume":"105","author":"E Chou","year":"2002","journal-title":"Circulation"},{"key":"pone.0254921.ref017","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1016\/S0002-9440(10)63821-7","article-title":"Cellular dysfunction in the diabetic fibroblast: impairment in migration, vascular endothelial growth factor production, and response to hypoxia","volume":"162","author":"OZ Lerman","year":"2003","journal-title":"Am J Pathol"},{"key":"pone.0254921.ref018","doi-asserted-by":"crossref","first-page":"13505","DOI":"10.1073\/pnas.0906670106","article-title":"The molecular basis for impaired hypoxia-induced VEGF expression in diabetic tissues","volume":"106","author":"H Thangarajah","year":"2009","journal-title":"ProcNatlAcadSci USA"},{"key":"pone.0254921.ref019","doi-asserted-by":"crossref","first-page":"721","DOI":"10.1038\/nrc1187","article-title":"Targeting HIF-1 for cancer therapy","volume":"3","author":"GL Semenza","year":"2003","journal-title":"Nat Rev Cancer"},{"key":"pone.0254921.ref020","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1038\/nature02871","article-title":"The functions of animal micro RNAs","volume":"431","author":"V Ambros","year":"2004","journal-title":"Nature"},{"key":"pone.0254921.ref021","first-page":"281","article-title":"Micro RNAs: genomics, biogenesis, mechanism, and function","volume":"136","author":"DP Bartel","year":"2004","journal-title":"Cell"},{"key":"pone.0254921.ref022","doi-asserted-by":"crossref","first-page":"704","DOI":"10.1038\/nrg2634","article-title":"Causes and consequences of microRNA dysregulation in cancer","volume":"10","author":"CM Croce","year":"2009","journal-title":"Nature Reviews Genetics"},{"key":"pone.0254921.ref023","doi-asserted-by":"crossref","first-page":"522","DOI":"10.1038\/nrg1379","article-title":") Micro RNAs: small RNAs with a big role in gene regulation","volume":"5","author":"L He","year":"2004","journal-title":"Nature Reviews Genetics"},{"key":"pone.0254921.ref024","doi-asserted-by":"crossref","first-page":"1519","DOI":"10.1126\/science.1111444","article-title":"Ribo-genome: the big world of small RNAs","volume":"309","author":"PD Zamore","year":"2005","journal-title":"Science"},{"key":"pone.0254921.ref025","author":"S Biswas","year":"2010","journal-title":"Hypoxia inducible microRNA 210 attenuates keratinocyte proliferation and impairs closure in a murine model of ischemic wounds"},{"issue":"11","key":"pone.0254921.ref026","doi-asserted-by":"crossref","first-page":"3821","DOI":"10.1093\/nar\/gkp255","article-title":"MicroRNA-338-3p and microRNA-451 contribute to the formation of basolateral polarity in epithelial cells","volume":"37","author":"S Tsuchiya","year":"2009","journal-title":"Nucleic Acids Research"},{"key":"pone.0254921.ref027","article-title":"Hypoxia Inducible Factor 1- alpha induces miR-210 in normoxic differentiating myoblasts","author":"L Cicchillitti","year":"2012","journal-title":"JBC"},{"key":"pone.0254921.ref028","author":"LB Nielsen","year":"2012","journal-title":"Circulating Levels of MicroRNA from Children with Newly Diagnosed Type 1 Diabetes and Healthy Controls: Evidence that miR-25 Associates to Residual Beta-Cell Function and Glycemic Control during Disease Progression Experimental Diabetes Research"},{"issue":"6","key":"pone.0254921.ref029","doi-asserted-by":"crossref","first-page":"e20980","DOI":"10.1371\/journal.pone.0020980","article-title":"Global MicroRNA Expression Profiling Identifies MiR-210 Associated with Tumor Proliferation, Invasion and Poor Clinical Outcome in Breast Cancer","volume":"6","author":"F Rothe","year":"2011","journal-title":"PLoS ONE"},{"issue":"3","key":"pone.0254921.ref030","article-title":"miR-210: The Master Hypoxamir","volume":"19","author":"YC Chan","year":"2012","journal-title":"Microcirculation"},{"key":"pone.0254921.ref031","first-page":"1","article-title":"The Evaluation and Treatment of Diabetic Foot Ulcers and Diabetic Foot Infections","volume":"11","author":"MA Del Core","year":"2018","journal-title":"Foot & Ankle Orthopaedics"},{"key":"pone.0254921.ref032","doi-asserted-by":"crossref","first-page":"1219","DOI":"10.1172\/JCI32169","article-title":"Cellular and molecular basis of wound healing in diabetes","volume":"117","author":"H. Brem","year":"2007","journal-title":"J Clin Invest"},{"key":"pone.0254921.ref033","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1016\/j.diabres.2015.05.014","article-title":"Impact of the hypoxia inducible factor-1alpha (HIF-1alpha) pro582serpolymorphism and its gene expression on diabetic foot ulcers","volume":"109","author":"S Pichu","year":"2015","journal-title":"Diabetes Res ClinPract"},{"key":"pone.0254921.ref034","doi-asserted-by":"crossref","first-page":"833","DOI":"10.1016\/j.ijbiomac.2018.08.011","article-title":"Association of hypoxia inducible factor-1 alpha exon 12 mutation in diabetic patients with and without diabetic foot ulcer.Int Journal of Biol","volume":"119","author":"S Pichu","year":"2018","journal-title":"Macromolecules"},{"key":"pone.0254921.ref035","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1093\/cvr\/cvr300","article-title":"Role of microRNAs in diabetes and its cardiovascular complications","volume":"93","author":"S Shantikumar","year":"2012","journal-title":"Cardiovascular Research"},{"key":"pone.0254921.ref036","article-title":"MicroRNAs and Diabetic complications","author":"R Natarajan","year":"2012","journal-title":"J. of Cardiovascular. Trans. Res"},{"key":"pone.0254921.ref037","doi-asserted-by":"crossref","first-page":"926","DOI":"10.3390\/genes5040926","article-title":"The role of Micro RNAs in diabetic complications\u2014Special emphasis on Wound Healing","author":"J Moura","year":"2014","journal-title":"Genes"},{"key":"pone.0254921.ref038","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1038\/jid.2010.268","article-title":"A comprehensive analysis of microRNA expression during human keratinocyte differentiationin vitro and in vivo","volume":"131","author":"J Hildebrand","year":"2011","journal-title":"J. Invest. Dermatol"},{"key":"pone.0254921.ref039","doi-asserted-by":"crossref","first-page":"2263","DOI":"10.1016\/j.febslet.2009.06.006","article-title":"Mir-210 promotes osteoblastic differentiation through inhibition of acvr1b","volume":"583","author":"Y Mizuno","year":"2009","journal-title":"FEBS Lett"},{"key":"pone.0254921.ref040","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1007\/978-1-4614-5915-6_10","article-title":"miR-210: Fine -Tuning the hypoxic response","volume":"772","author":"M Ivan","year":"2014","journal-title":"AdvExp Med Biol."},{"key":"pone.0254921.ref041","article-title":"Role of VHL, HIF1A and SDH on the expression of miR-210: Implications for tumoral pseudo-hypoxic fate","volume":"8","author":"A Merlo","year":"2016","journal-title":"Oncotarget."},{"key":"pone.0254921.ref042","doi-asserted-by":"crossref","first-page":"753","DOI":"10.1016\/j.imbio.2011.01.001","article-title":"Macrophages in skin injury and repair","volume":"216","author":"B.M. Delavary","year":"2011","journal-title":"Immunobiology"},{"key":"pone.0254921.ref043","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1111\/j.1524-475X.2007.00271.x","article-title":"Agent-based model of inflammation and wound healing: Insights into diabetic foot ulcer pathology and the role of transforming growth factor-beta1","volume":"15","author":"Q. Mi","year":"2007","journal-title":"Wound Repair Regener"},{"key":"pone.0254921.ref044","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1016\/j.ijbiomac.2017.05.050","article-title":"Impact of lysyl oxidase (G473A) polymorphism on diabetic foot ulcers","volume":"103","author":"S Pichu","year":"2017","journal-title":"Int J Biol Macromol"},{"key":"pone.0254921.ref045","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1016\/j.ijbiomac.2017.12.070","article-title":"Unmethylated promoter DNA correlates with p53 expression and apoptotic levels only in Vitamin B9 and B12 deficient megaloblastic anemia but not in non-megaloblastic anemia controls","volume":"109","author":"MK Yadav","year":"2018","journal-title":"Int J Biol Macromol"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0254921","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,7,22]],"date-time":"2021-07-22T13:45:36Z","timestamp":1626961536000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0254921"}},"subtitle":[],"editor":[{"given":"Kanhaiya","family":"Singh","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2021,7,22]]},"references-count":45,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2021,7,22]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0254921","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,7,22]]}}}