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Recent studies have shown that N\u2010myc downstream regulated gene 2 (NDRG2) exerts a neuroprotective effect on the brain and spinal cord. In addition, our previous studies have confirmed that NDRG2 is expressed in mouse retinal photoreceptors and counteracts\n                    <jats:italic>N<\/jats:italic>\n                    \u2010methyl\u2010\n                    <jats:italic>N<\/jats:italic>\n                    \u2010nitrosourea (MNU)\u2010induced apoptosis. However, the underlying molecular mechanism remains unclear. In this study, we observed that the expression of NDRG2 was not only significantly inhibited in photoreceptors after MNU treatment but also after hydrogen peroxide treatment, and photoreceptor apoptosis was alleviated or aggravated after overexpression or knockdown of\n                    <jats:italic>NDRG2<\/jats:italic>\n                    in the 661W photoreceptor cell line, respectively. The apoptosis inhibitor Z\u2010VAD\u2010FMK rescued photoreceptor apoptosis induced by MNU after\n                    <jats:italic>NDRG2<\/jats:italic>\n                    knockdown. Next, we screened and identified tissue inhibitor of metalloproteinases 3 (TIMP3) as the downstream molecule of NDRG2 in 661W cells by using quantitative real\u2010time polymerase chain reaction. TIMP3 exerts a neuroprotective effect by inhibiting the expression of matrix metalloproteinases (MMPs). Subsequently, we found that signal transducer and activator of transcription 3 (STAT3) mediated the NDRG2\u2010associated regulation of TIMP3. Finally, we overexpressed\n                    <jats:italic>NDRG2<\/jats:italic>\n                    in mouse retinal tissues by intravitreally injecting an adeno\u2010associated virus with mouse\n                    <jats:italic>NDRG2 in\u2009vivo<\/jats:italic>\n                    . Results showed that NDRG2 upregulated the expression of phospho\u2010STAT3 (p\u2010STAT3) and TIMP3, while suppressing MNU\u2010induced photoreceptor apoptosis and MMP expression. Our findings revealed how NDRG2 regulates the STAT3\/TIMP3\/MMP pathway and uncovered the molecular mechanism underlying its neuroprotective effect on mouse retinal photoreceptors.\n                  <\/jats:p>","DOI":"10.1111\/febs.17021","type":"journal-article","created":{"date-parts":[[2023,11,30]],"date-time":"2023-11-30T23:38:10Z","timestamp":1701387490000},"page":"986-1007","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["NDRG2 alleviates photoreceptor apoptosis by regulating the STAT3\/TIMP3\/MMP pathway in mice with retinal degenerative disease"],"prefix":"10.1111","volume":"291","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0996-3738","authenticated-orcid":false,"given":"Tao","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Institute of Molecular and Translational Medicine Xi'an Jiaotong University  China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yecheng","family":"Xiong","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Institute of Molecular and Translational Medicine Xi'an Jiaotong University  China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chunlei","family":"Deng","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Institute of Molecular and Translational Medicine Xi'an Jiaotong University  China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chengbiao","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Institute of Molecular and Translational Medicine Xi'an Jiaotong University  China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mengxing","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Institute of Molecular and Translational Medicine Xi'an Jiaotong University  China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rui","family":"Quan","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Institute of Molecular and Translational Medicine Xi'an Jiaotong University  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