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We demonstrated that exogenous T\u03b24 treatment up\u2010regulated the expression of the miR\u2010200a <jats:italic>in\u00a0vitro<\/jats:italic> in rat brain progenitor cells and <jats:italic>in\u00a0vivo<\/jats:italic> in the peri\u2010infarct area of rats subjected to middle cerebral artery occlusion (<jats:styled-content style=\"fixed-case\">MCAO<\/jats:styled-content>). The up\u2010regulation of miR\u2010200a down\u2010regulated the expression of the following targets <jats:italic>in\u00a0vitro<\/jats:italic> and <jats:italic>in\u00a0vivo<\/jats:italic> models: (i) growth factor receptor\u2010bound protein 2 (Grb2), an adaptor protein involved in epidermal growth factor receptor (<jats:styled-content style=\"fixed-case\">EGFR<\/jats:styled-content>)\/Grb2\/Ras\/<jats:styled-content style=\"fixed-case\">MEK<\/jats:styled-content>\/<jats:styled-content style=\"fixed-case\">ERK<\/jats:styled-content>1\/c\u2010Jun signaling pathway, which negatively regulates the expression of myelin basic protein (MBP), a marker of mature oligodendrocyte; (ii) <jats:styled-content style=\"fixed-case\">ERRFI<\/jats:styled-content>\u20101\/Mig\u20106, an endogenous potent kinase inhibitor of <jats:styled-content style=\"fixed-case\">EGFR<\/jats:styled-content>, which resulted in activation\/phosphorylation of <jats:styled-content style=\"fixed-case\">EGFR<\/jats:styled-content>; (iii) friend of <jats:styled-content style=\"fixed-case\">GATA<\/jats:styled-content> 2, and phosphatase and tensin homolog deleted in chromosome 10 (<jats:styled-content style=\"fixed-case\">PTEN<\/jats:styled-content>), which are potent inhibitors of the phosphatidylinositol\u20103\u2010kinase (<jats:styled-content style=\"fixed-case\">PI<\/jats:styled-content>3K)\/<jats:styled-content style=\"fixed-case\">AKT<\/jats:styled-content> signaling pathway, and resulted in marked activation of <jats:styled-content style=\"fixed-case\">AKT<\/jats:styled-content>; and (iv) transcription factor, p53, which induces pro\u2010apoptotic genes, and possibly reduced apoptosis of the progenitor cells subjected to oxygen glucose deprivation (OGD). Anti\u2010miR\u2010200a transfection reversed all the effects of T\u03b24 treatment <jats:italic>in\u00a0vitro<\/jats:italic>. Thus, T\u03b24 up\u2010regulated MBP synthesis, and inhibited OGD\u2010induced apoptosis in a novel miR\u2010200a dependent <jats:styled-content style=\"fixed-case\">EGFR<\/jats:styled-content> signaling pathway. Our findings of miR\u2010200a\u2010mediated protection of progenitor cells may provide a new therapeutic importance for the treatment of neurologic injury.<\/jats:p><\/jats:sec><jats:sec><jats:label\/><jats:p>\n<jats:boxed-text content-type=\"graphic\" position=\"anchor\"><jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/jnc13394-fig-0008-m.png\"><jats:alt-text>image<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text>\nT\u03b24\u2010induced micro\u2010RNA\u2010200a (miR\u2010200a) regulates EGFR signaling pathways for MBP synthesis and apoptosis: up\u2010regulation of miR\u2010200a after T\u03b24 treatment, increases MBP synthesis after targeting Grb2 and thereby inactivating c\u2010Jun from inhibition of MBP synthesis; and also inhibits OGD\u2010mediated apoptosis after targeting EGFR inhibitor (Mig\u20106), PI3K inhibitors (FOG2 and Pten) and an inducer (p53) of pro\u2010apoptotic genes, for AKT activation and down\u2010regulation of p53. These findings may contribute the therapeutic benefits for stroke and other neuronal diseases associated with demyelination disorders.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jnc.13394","type":"journal-article","created":{"date-parts":[[2015,10,14]],"date-time":"2015-10-14T15:17:20Z","timestamp":1444835840000},"page":"118-132","source":"Crossref","is-referenced-by-count":33,"title":["Thymosin beta 4 up\u2010regulates miR\u2010200a expression and induces differentiation and survival of rat brain progenitor cells"],"prefix":"10.1111","volume":"136","author":[{"given":"Manoranjan","family":"Santra","sequence":"first","affiliation":[{"name":"Department of Neurology Henry Ford Health System Detroit Michigan USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Chopp","sequence":"additional","affiliation":[{"name":"Department of Neurology Henry Ford Health System Detroit Michigan USA"},{"name":"Department of Physics Oakland University Rochester Michigan USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sutapa","family":"Santra","sequence":"additional","affiliation":[{"name":"Department of Neurology Henry Ford Health System Detroit Michigan USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ankita","family":"Nallani","sequence":"additional","affiliation":[{"name":"Department of Neurology Henry Ford Health System Detroit Michigan USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shivam","family":"Vyas","sequence":"additional","affiliation":[{"name":"Department of Neurology Henry Ford Health System Detroit Michigan USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zheng Gang","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Neurology Henry Ford Health System Detroit Michigan USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel C.","family":"Morris","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine Henry Ford Health System Detroit Michigan USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2015,11,10]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-08-2245"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1017\/S1740925X08000082"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2981-05.2005"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn1938"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature09347"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm747"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0075517"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-8993(98)00286-8"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.2001.81.2.871"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0048474"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/bgu202"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2007.149"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2546-10.2010"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2007.11.018"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-291X(92)91859-O"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.19-18-07860.1999"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2114-04.2004"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/jcbfm.1994.119"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1460-9568.2011.07616.x"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/379557a0"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2009.07.015"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(02)01133-9"},{"key":"e_1_2_7_24_1","doi-asserted-by":"crossref","first-page":"7622","DOI":"10.1523\/JNEUROSCI.20-20-07622.2000","article-title":"Akt\u2010mediated survival of oligodendrocytes induced by neuregulins","volume":"20","author":"Flores A. 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