Unveiling the role of transgelin as a prognostic and therapeutic target in kidney fibrosis via a proteomic approach
Abstract Chronic kidney disease (CKD) progression involves tubulointerstitial fibrosis, a process characterized by excessive extracellular matrix accumulation. To identify potential biomarkers for kidney fibrosis, we performed mass spectrometry-based proteomic profiling of human kidney tubular epith...
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Nature Publishing Group
2024-10-01
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| Series: | Experimental and Molecular Medicine |
| Online Access: | https://doi.org/10.1038/s12276-024-01319-7 |
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| author | Soie Kwon Seongmin Cheon Kyu-Hong Kim Areum Seo Eunjin Bae Jae Wook Lee Ran-Hui Cha Jin Ho Hwang Yong Chul Kim Dong Ki Kim Yon Su Kim Dohyun Han Seung-Hee Yang |
| author_facet | Soie Kwon Seongmin Cheon Kyu-Hong Kim Areum Seo Eunjin Bae Jae Wook Lee Ran-Hui Cha Jin Ho Hwang Yong Chul Kim Dong Ki Kim Yon Su Kim Dohyun Han Seung-Hee Yang |
| author_sort | Soie Kwon |
| collection | DOAJ |
| description | Abstract Chronic kidney disease (CKD) progression involves tubulointerstitial fibrosis, a process characterized by excessive extracellular matrix accumulation. To identify potential biomarkers for kidney fibrosis, we performed mass spectrometry-based proteomic profiling of human kidney tubular epithelial cells and kidney tissue from a 5/6 nephrectomy rat model. Multidisciplinary analysis across kidney fibrosis models revealed 351 differentially expressed proteins associated with kidney fibrosis, and they were enriched in processes related to the extracellular matrix, kidney aging, and mitochondrial functions. Network analysis of the selected proteins revealed five crucial proteins, of which transgelin emerged as a candidate protein that interacts with known fibrosis-related proteins. Concordantly, the gene expression of transgelin in the kidney tissue from the 5/6 nephrectomy model was elevated. Transgelin expression in kidney tissue gradually increased from intermediate to advanced fibrosis stages in 5/6 Nx rats and mice with unilateral ureteral obstruction. Subsequent validation in kidney tissue and urine samples from patients with CKD confirmed the upregulation of transgelin, particularly under advanced disease stages. Moreover, we investigated whether blocking TAGLN ameliorated kidney fibrosis and reduced reactive oxygen species levels in cellular models. In conclusion, our proteomic approach identified TAGLN as a potential noninvasive biomarker and therapeutic target for CKD-associated kidney fibrosis, suggesting its role in modulating mitochondrial dysfunction and oxidative stress responses. |
| format | Article |
| id | doaj-art-1670cf81393b484b8a916569bbaa7495 |
| institution | Kabale University |
| issn | 2092-6413 |
| language | English |
| publishDate | 2024-10-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Experimental and Molecular Medicine |
| spelling | doaj-art-1670cf81393b484b8a916569bbaa74952024-11-10T12:09:52ZengNature Publishing GroupExperimental and Molecular Medicine2092-64132024-10-0156102296230810.1038/s12276-024-01319-7Unveiling the role of transgelin as a prognostic and therapeutic target in kidney fibrosis via a proteomic approachSoie Kwon0Seongmin Cheon1Kyu-Hong Kim2Areum Seo3Eunjin Bae4Jae Wook Lee5Ran-Hui Cha6Jin Ho Hwang7Yong Chul Kim8Dong Ki Kim9Yon Su Kim10Dohyun Han11Seung-Hee Yang12Department of Internal Medicine, Chung-Ang University HospitalSchool of Biological Sciences and Technology, Chonnam National UniversityKidney Research Institute, Seoul National University College of MedicineKidney Research Institute, Seoul National University College of MedicineDepartment of Internal Medicine, Gyeongsang National University College of Medicine, Gyeongsang University Changwon HospitalNephrology Clinic, National Cancer Center of KoreaBiomedical Research Institute, Seoul National University HospitalDepartment of Internal Medicine, Chung-Ang University HospitalDepartment of Internal Medicine, Seoul National University HospitalDepartment of Internal Medicine, Seoul National University HospitalKidney Research Institute, Seoul National University College of MedicineProteomics Core Facility, Biomedical Research Institute, Seoul National University HospitalKidney Research Institute, Seoul National University College of MedicineAbstract Chronic kidney disease (CKD) progression involves tubulointerstitial fibrosis, a process characterized by excessive extracellular matrix accumulation. To identify potential biomarkers for kidney fibrosis, we performed mass spectrometry-based proteomic profiling of human kidney tubular epithelial cells and kidney tissue from a 5/6 nephrectomy rat model. Multidisciplinary analysis across kidney fibrosis models revealed 351 differentially expressed proteins associated with kidney fibrosis, and they were enriched in processes related to the extracellular matrix, kidney aging, and mitochondrial functions. Network analysis of the selected proteins revealed five crucial proteins, of which transgelin emerged as a candidate protein that interacts with known fibrosis-related proteins. Concordantly, the gene expression of transgelin in the kidney tissue from the 5/6 nephrectomy model was elevated. Transgelin expression in kidney tissue gradually increased from intermediate to advanced fibrosis stages in 5/6 Nx rats and mice with unilateral ureteral obstruction. Subsequent validation in kidney tissue and urine samples from patients with CKD confirmed the upregulation of transgelin, particularly under advanced disease stages. Moreover, we investigated whether blocking TAGLN ameliorated kidney fibrosis and reduced reactive oxygen species levels in cellular models. In conclusion, our proteomic approach identified TAGLN as a potential noninvasive biomarker and therapeutic target for CKD-associated kidney fibrosis, suggesting its role in modulating mitochondrial dysfunction and oxidative stress responses.https://doi.org/10.1038/s12276-024-01319-7 |
| spellingShingle | Soie Kwon Seongmin Cheon Kyu-Hong Kim Areum Seo Eunjin Bae Jae Wook Lee Ran-Hui Cha Jin Ho Hwang Yong Chul Kim Dong Ki Kim Yon Su Kim Dohyun Han Seung-Hee Yang Unveiling the role of transgelin as a prognostic and therapeutic target in kidney fibrosis via a proteomic approach Experimental and Molecular Medicine |
| title | Unveiling the role of transgelin as a prognostic and therapeutic target in kidney fibrosis via a proteomic approach |
| title_full | Unveiling the role of transgelin as a prognostic and therapeutic target in kidney fibrosis via a proteomic approach |
| title_fullStr | Unveiling the role of transgelin as a prognostic and therapeutic target in kidney fibrosis via a proteomic approach |
| title_full_unstemmed | Unveiling the role of transgelin as a prognostic and therapeutic target in kidney fibrosis via a proteomic approach |
| title_short | Unveiling the role of transgelin as a prognostic and therapeutic target in kidney fibrosis via a proteomic approach |
| title_sort | unveiling the role of transgelin as a prognostic and therapeutic target in kidney fibrosis via a proteomic approach |
| url | https://doi.org/10.1038/s12276-024-01319-7 |
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