Network-based identification and prioritization of key transcriptional factors of diabetic kidney disease
<p>Diabetic nephropathy (DN) is one of the most established microvascular complications of diabetes and a key cause of end-stage renal disease. It is well established that gene susceptibility to DN plays a critical role in disease pathophysiology. Therefore, many genetic studies have been perf...
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| مؤلفون آخرون: | , , , , , , , , |
| منشور في: |
2023
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| _version_ | 1864513508052303872 |
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| author | Ikhlak Ahmed (150200) |
| author2 | Mubarak Ziab (15430083) Sahar Da’as (15430086) Waseem Hasan (17280670) Sujitha P. Jeya (15430110) Elbay Aliyev (14056972) Sabah Nisar (12561961) Ajaz A. Bhat (12984701) Khalid Adnan Fakhro (17316958) Ammira S. Alshabeeb Akil (17807627) |
| author2_role | author author author author author author author author author |
| author_facet | Ikhlak Ahmed (150200) Mubarak Ziab (15430083) Sahar Da’as (15430086) Waseem Hasan (17280670) Sujitha P. Jeya (15430110) Elbay Aliyev (14056972) Sabah Nisar (12561961) Ajaz A. Bhat (12984701) Khalid Adnan Fakhro (17316958) Ammira S. Alshabeeb Akil (17807627) |
| author_role | author |
| dc.creator.none.fl_str_mv | Ikhlak Ahmed (150200) Mubarak Ziab (15430083) Sahar Da’as (15430086) Waseem Hasan (17280670) Sujitha P. Jeya (15430110) Elbay Aliyev (14056972) Sabah Nisar (12561961) Ajaz A. Bhat (12984701) Khalid Adnan Fakhro (17316958) Ammira S. Alshabeeb Akil (17807627) |
| dc.date.none.fl_str_mv | 2023-01-04T03:00:00Z |
| dc.identifier.none.fl_str_mv | 10.1016/j.csbj.2022.12.054 |
| dc.relation.none.fl_str_mv | https://figshare.com/articles/journal_contribution/Network-based_identification_and_prioritization_of_key_transcriptional_factors_of_diabetic_kidney_disease/26661625 |
| dc.rights.none.fl_str_mv | CC BY 4.0 info:eu-repo/semantics/openAccess |
| dc.subject.none.fl_str_mv | Biological sciences Genetics Biomedical and clinical sciences Clinical sciences Medical biochemistry and metabolomics Diabetic nephropathy Diabetic kidney disease Gene expression Network analysis Hyperglycemic zebrafish Transcription factors DACH1LMX1BWT Therapeutic biomarkers |
| dc.title.none.fl_str_mv | Network-based identification and prioritization of key transcriptional factors of diabetic kidney disease |
| dc.type.none.fl_str_mv | Text Journal contribution info:eu-repo/semantics/publishedVersion text contribution to journal |
| description | <p>Diabetic nephropathy (DN) is one of the most established microvascular complications of diabetes and a key cause of end-stage renal disease. It is well established that gene susceptibility to DN plays a critical role in disease pathophysiology. Therefore, many genetic studies have been performed to categorize candidate genes in prominent diabetic cohorts, aiming to investigate DN pathogenesis and etiology. In this study, we performed a meta-analysis on the expression profiles of GSE1009, GSE30122, GSE96804, GSE99340, GSE104948, GSE104954, and GSE111154 to identify critical transcriptional factors associated with DN progression. The analysis was conducted for all individual datasets for each kidney tissue (glomerulus, tubules, and kidney cortex). We identified distinct clusters of susceptibility genes that were dysregulated in a renal compartment-specific pattern. Further, we recognized a small but a closely connected set of these susceptibility genes enriched for podocyte differentiation, several of which were characterized as genes encoding critical transcriptional factors (TFs) involved in DN development and podocyte function. To validate the role of identified TFs in DN progression, we functionally validated the three main TFs (DACH1, LMX1B, and WT1) identified through differential gene expression and network analysis using the hyperglycemic zebrafish model. We report that hyperglycemia-induced altered gene expression of the key TF genes leads to morphological abnormalities in zebrafish glomeruli, pronephric tubules, proximal and distal ducts. This study demonstrated that altered expression of these TF genes could be associated with hyperglycemia-induced nephropathy and, thus, aids in understanding the molecular drivers, essential genes, and pathways that trigger DN initiation and development.</p><h2>Other Information</h2> <p> Published in: Computational and Structural Biotechnology Journal<br> License: <a href="http://creativecommons.org/licenses/by/4.0/" target="_blank">http://creativecommons.org/licenses/by/4.0/</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.1016/j.csbj.2022.12.054" target="_blank">https://dx.doi.org/10.1016/j.csbj.2022.12.054</a></p> |
| eu_rights_str_mv | openAccess |
| id | Manara2_91c1272e9b247b87a489ecd3ab250082 |
| identifier_str_mv | 10.1016/j.csbj.2022.12.054 |
| network_acronym_str | Manara2 |
| network_name_str | Manara2 |
| oai_identifier_str | oai:figshare.com:article/26661625 |
| publishDate | 2023 |
| repository.mail.fl_str_mv | |
| repository.name.fl_str_mv | |
| repository_id_str | |
| rights_invalid_str_mv | CC BY 4.0 |
| spelling | Network-based identification and prioritization of key transcriptional factors of diabetic kidney diseaseIkhlak Ahmed (150200)Mubarak Ziab (15430083)Sahar Da’as (15430086)Waseem Hasan (17280670)Sujitha P. Jeya (15430110)Elbay Aliyev (14056972)Sabah Nisar (12561961)Ajaz A. Bhat (12984701)Khalid Adnan Fakhro (17316958)Ammira S. Alshabeeb Akil (17807627)Biological sciencesGeneticsBiomedical and clinical sciencesClinical sciencesMedical biochemistry and metabolomicsDiabetic nephropathyDiabetic kidney diseaseGene expressionNetwork analysisHyperglycemic zebrafishTranscription factorsDACH1LMX1BWTTherapeutic biomarkers<p>Diabetic nephropathy (DN) is one of the most established microvascular complications of diabetes and a key cause of end-stage renal disease. It is well established that gene susceptibility to DN plays a critical role in disease pathophysiology. Therefore, many genetic studies have been performed to categorize candidate genes in prominent diabetic cohorts, aiming to investigate DN pathogenesis and etiology. In this study, we performed a meta-analysis on the expression profiles of GSE1009, GSE30122, GSE96804, GSE99340, GSE104948, GSE104954, and GSE111154 to identify critical transcriptional factors associated with DN progression. The analysis was conducted for all individual datasets for each kidney tissue (glomerulus, tubules, and kidney cortex). We identified distinct clusters of susceptibility genes that were dysregulated in a renal compartment-specific pattern. Further, we recognized a small but a closely connected set of these susceptibility genes enriched for podocyte differentiation, several of which were characterized as genes encoding critical transcriptional factors (TFs) involved in DN development and podocyte function. To validate the role of identified TFs in DN progression, we functionally validated the three main TFs (DACH1, LMX1B, and WT1) identified through differential gene expression and network analysis using the hyperglycemic zebrafish model. We report that hyperglycemia-induced altered gene expression of the key TF genes leads to morphological abnormalities in zebrafish glomeruli, pronephric tubules, proximal and distal ducts. This study demonstrated that altered expression of these TF genes could be associated with hyperglycemia-induced nephropathy and, thus, aids in understanding the molecular drivers, essential genes, and pathways that trigger DN initiation and development.</p><h2>Other Information</h2> <p> Published in: Computational and Structural Biotechnology Journal<br> License: <a href="http://creativecommons.org/licenses/by/4.0/" target="_blank">http://creativecommons.org/licenses/by/4.0/</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.1016/j.csbj.2022.12.054" target="_blank">https://dx.doi.org/10.1016/j.csbj.2022.12.054</a></p>2023-01-04T03:00:00ZTextJournal contributioninfo:eu-repo/semantics/publishedVersiontextcontribution to journal10.1016/j.csbj.2022.12.054https://figshare.com/articles/journal_contribution/Network-based_identification_and_prioritization_of_key_transcriptional_factors_of_diabetic_kidney_disease/26661625CC BY 4.0info:eu-repo/semantics/openAccessoai:figshare.com:article/266616252023-01-04T03:00:00Z |
| spellingShingle | Network-based identification and prioritization of key transcriptional factors of diabetic kidney disease Ikhlak Ahmed (150200) Biological sciences Genetics Biomedical and clinical sciences Clinical sciences Medical biochemistry and metabolomics Diabetic nephropathy Diabetic kidney disease Gene expression Network analysis Hyperglycemic zebrafish Transcription factors DACH1LMX1BWT Therapeutic biomarkers |
| status_str | publishedVersion |
| title | Network-based identification and prioritization of key transcriptional factors of diabetic kidney disease |
| title_full | Network-based identification and prioritization of key transcriptional factors of diabetic kidney disease |
| title_fullStr | Network-based identification and prioritization of key transcriptional factors of diabetic kidney disease |
| title_full_unstemmed | Network-based identification and prioritization of key transcriptional factors of diabetic kidney disease |
| title_short | Network-based identification and prioritization of key transcriptional factors of diabetic kidney disease |
| title_sort | Network-based identification and prioritization of key transcriptional factors of diabetic kidney disease |
| topic | Biological sciences Genetics Biomedical and clinical sciences Clinical sciences Medical biochemistry and metabolomics Diabetic nephropathy Diabetic kidney disease Gene expression Network analysis Hyperglycemic zebrafish Transcription factors DACH1LMX1BWT Therapeutic biomarkers |