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<PubmedArticle><MedlineCitation Status="PubMed-not-MEDLINE" Owner="NLM"><PMID Version="1">37842165</PMID><DateRevised><Year>2023</Year><Month>10</Month><Day>20</Day></DateRevised><Article PubModel="Electronic-eCollection"><Journal><ISSN IssnType="Print">2162-2531</ISSN><JournalIssue CitedMedium="Print"><Volume>34</Volume><PubDate><Year>2023</Year><Month>Dec</Month><Day>12</Day></PubDate></JournalIssue><Title>Molecular therapy. Nucleic acids</Title><ISOAbbreviation>Mol Ther Nucleic Acids</ISOAbbreviation></Journal><ArticleTitle>A mutual regulatory loop between miR-155 and SOCS1 influences renal inflammation and diabetic kidney disease.</ArticleTitle><Pagination><StartPage>102041</StartPage><MedlinePgn>102041</MedlinePgn></Pagination><ELocationID EIdType="pii" ValidYN="Y">102041</ELocationID><ELocationID EIdType="doi" ValidYN="Y">10.1016/j.omtn.2023.102041</ELocationID><Abstract><AbstractText>Diabetic kidney disease (DKD) is a common microvascular complication of diabetes, a global health issue. Hyperglycemia, in concert with cytokines, activates the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway to induce inflammation and oxidative stress contributing to renal damage. There is evidence of microRNA-155 (miR-155) involvement in diabetes complications, but the underlying mechanisms are unclear. In this study, gain- and loss-of-function experiments were conducted to investigate the interplay between miR-155-5p and suppressor of cytokine signaling 1 (SOCS1) in the regulation of the JAK/STAT pathway during renal inflammation and DKD. In experimental models of mesangial injury and diabetes, miR-155-5p expression correlated inversely with SOCS1 and positively with albuminuria and expression levels of cytokines and prooxidant genes. In renal cells, miR-155-5p mimic downregulated SOCS1 and promoted STAT1/3 activation, cytokine expression, and cell proliferation and migration. Conversely, both miR-155-5p antagonism and SOCS1 overexpression protected cells from inflammation and hyperglycemia damage. <i>In&#xa0;vivo</i>, SOCS1 gene delivery decreased miR-155-5p and kidney injury in diabetic mice. Moreover, therapeutic inhibition of miR-155-5p suppressed STAT1/3 activation and alleviated albuminuria, mesangial damage, and renal expression of inflammatory and fibrotic genes. In conclusion, modulation of the miR-155/SOCS1 axis protects kidneys against diabetic damage, thus highlighting its potential as therapeutic target for DKD.</AbstractText><CopyrightInformation>&#xa9; 2023 The Author(s).</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Prieto</LastName><ForeName>Ignacio</ForeName><Initials>I</Initials><AffiliationInfo><Affiliation>Renal, Vascular and Diabetes Research Lab, Instituto de Investigaciones Sanitarias-Fundacion Jimenez Diaz (IIS-FJD), Universidad Autonoma de Madrid (UAM), 28040 Madrid, Spain.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Spanish Biomedical Research Centre in Diabetes and Associated Metabolic Disorders (CIBERDEM), 28029 Madrid, Spain.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Kavanagh</LastName><ForeName>Mar&#xed;a</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Renal, Vascular and Diabetes Research Lab, Instituto de Investigaciones Sanitarias-Fundacion Jimenez Diaz (IIS-FJD), Universidad Autonoma de Madrid (UAM), 28040 Madrid, Spain.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Jimenez-Castilla</LastName><ForeName>Luna</ForeName><Initials>L</Initials><AffiliationInfo><Affiliation>Renal, Vascular and Diabetes Research Lab, Instituto de Investigaciones Sanitarias-Fundacion Jimenez Diaz (IIS-FJD), Universidad Autonoma de Madrid (UAM), 28040 Madrid, Spain.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Spanish Biomedical Research Centre in Diabetes and Associated Metabolic Disorders (CIBERDEM), 28029 Madrid, Spain.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Pardines</LastName><ForeName>Marisa</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Renal, Vascular and Diabetes Research Lab, Instituto de Investigaciones Sanitarias-Fundacion Jimenez Diaz (IIS-FJD), Universidad Autonoma de Madrid (UAM), 28040 Madrid, Spain.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Lazaro</LastName><ForeName>Iolanda</ForeName><Initials>I</Initials><AffiliationInfo><Affiliation>Cardiovascular Risk and Nutrition, Hospital del Mar Medical Research Institute-IMIM, 08003 Barcelona, Spain.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Herrero Del Real</LastName><ForeName>Isabel</ForeName><Initials>I</Initials><AffiliationInfo><Affiliation>Renal, Vascular and Diabetes Research Lab, Instituto de Investigaciones Sanitarias-Fundacion Jimenez Diaz (IIS-FJD), Universidad Autonoma de Madrid (UAM), 28040 Madrid, Spain.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Flores-Mu&#xf1;oz</LastName><ForeName>Monica</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Translational Medicine Lab, Instituto de Ciencias de la Salud, Universidad Veracruzana, Xalapa 91140, Veracruz, Mexico.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Egido</LastName><ForeName>Jesus</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>Renal, Vascular and Diabetes Research Lab, Instituto de Investigaciones Sanitarias-Fundacion Jimenez Diaz (IIS-FJD), Universidad Autonoma de Madrid (UAM), 28040 Madrid, Spain.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Spanish Biomedical Research Centre in Diabetes and Associated Metabolic Disorders (CIBERDEM), 28029 Madrid, Spain.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Lopez-Franco</LastName><ForeName>Oscar</ForeName><Initials>O</Initials><AffiliationInfo><Affiliation>Translational Medicine Lab, Instituto de Ciencias de la Salud, Universidad Veracruzana, Xalapa 91140, Veracruz, Mexico.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Gomez-Guerrero</LastName><ForeName>Carmen</ForeName><Initials>C</Initials><AffiliationInfo><Affiliation>Renal, Vascular and Diabetes Research Lab, Instituto de Investigaciones Sanitarias-Fundacion Jimenez Diaz (IIS-FJD), Universidad Autonoma de Madrid (UAM), 28040 Madrid, Spain.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Spanish Biomedical Research Centre in Diabetes and Associated Metabolic Disorders (CIBERDEM), 28029 Madrid, Spain.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2023</Year><Month>09</Month><Day>27</Day></ArticleDate></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>Mol Ther Nucleic Acids</MedlineTA><NlmUniqueID>101581621</NlmUniqueID><ISSNLinking>2162-2531</ISSNLinking></MedlineJournalInfo><KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="N">JAK/STAT/SOCS</Keyword><Keyword MajorTopicYN="N">MT: Non-coding RNAs: diabetes</Keyword><Keyword MajorTopicYN="N">cytokines</Keyword><Keyword MajorTopicYN="N">diabetic kidney disease</Keyword><Keyword MajorTopicYN="N">fibrosis</Keyword><Keyword MajorTopicYN="N">hyperglycemia</Keyword><Keyword MajorTopicYN="N">microRNA</Keyword><Keyword MajorTopicYN="N">renal inflammation</Keyword><Keyword MajorTopicYN="N">signal transduction</Keyword></KeywordList><CoiStatement>All the authors declared no competing interests.</CoiStatement></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2023</Year><Month>4</Month><Day>28</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2023</Year><Month>9</Month><Day>23</Day></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2023</Year><Month>10</Month><Day>16</Day><Hour>6</Hour><Minute>49</Minute></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2023</Year><Month>10</Month><Day>16</Day><Hour>6</Hour><Minute>48</Minute></PubMedPubDate><PubMedPubDate 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