Glomerular proteomic profiling reveals early differences between preexisting and de novo type 2 diabetes in human renal allografts
Abstract Background Diabetes mellitus (DM), either preexisting or developing after transplantation, remains a crucial clinical problem in kidney transplantation. To obtain insights into the molecular mechanisms underlying PTDM development and early glomerular damage before the development of histolo...
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| Format: | Article |
| Language: | English |
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BMC
2023-08-01
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| Series: | BMC Nephrology |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12882-023-03294-z |
| _version_ | 1797577541698977792 |
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| author | Anne Kipp Hans-Peter Marti Janka Babickova Sigrid Nakken Sabine Leh Thea A. S. Halden Trond Jenssen Bjørn Egil Vikse Anders Åsberg Giulio Spagnoli Jessica Furriol |
| author_facet | Anne Kipp Hans-Peter Marti Janka Babickova Sigrid Nakken Sabine Leh Thea A. S. Halden Trond Jenssen Bjørn Egil Vikse Anders Åsberg Giulio Spagnoli Jessica Furriol |
| author_sort | Anne Kipp |
| collection | DOAJ |
| description | Abstract Background Diabetes mellitus (DM), either preexisting or developing after transplantation, remains a crucial clinical problem in kidney transplantation. To obtain insights into the molecular mechanisms underlying PTDM development and early glomerular damage before the development of histologically visible diabetic kidney disease, we comparatively analysed the proteome of histologically normal glomeruli from patients with PTDM and normoglycaemic (NG) transplant recipients. Moreover, to assess specificities inherent in PTDM, we also comparatively evaluated glomerular proteomes from transplant recipients with preexisting type 2 DM (T2DM). Methods Protocol biopsies were obtained from adult NG, PTDM and T2DM patients one year after kidney transplantation. Biopsies were formalin-fixed and embedded in paraffin, and glomerular cross-sections were microdissected. A total of 4 NG, 7 PTDM and 6 T2DM kidney biopsies were used for the analysis. The proteome was determined by liquid chromatography-tandem mass spectrometry. Relative differences in protein abundance and significantly dysregulated pathways were analysed. Results Proteins involved in cell adhesion, immune response, leukocyte transendothelial filtration, and cell localization and organization were less abundant in glomeruli from PTDM patients than in those from NG patients, and proteins associated with supramolecular fibre organization and protein-containing complex binding were more abundant in PTDM patients. Overall, proteins related to adherens and tight junctions and those related to the immune system, including leukocyte transendothelial migration, were more abundant in NG patients than in transplanted patients with DM, irrespective of the timing of its development. However, proteins included in cell‒cell junctions and adhesion, insulin resistance, and vesicle-mediated transport were all less abundant in PTDM patients than in T2DM patients. Conclusions The glomerular proteome profile differentiates PTDM from NG and T2DM, suggesting specific pathogenetic mechanisms. Further studies are warranted to validate these results, potentially leading to an improved understanding of PTDM kidney transplant pathophysiology and to the identification of novel biomarkers. |
| first_indexed | 2024-03-10T22:09:48Z |
| format | Article |
| id | doaj.art-df15af6c0222407f83ce8558b2e5a24e |
| institution | Directory Open Access Journal |
| issn | 1471-2369 |
| language | English |
| last_indexed | 2024-03-10T22:09:48Z |
| publishDate | 2023-08-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Nephrology |
| spelling | doaj.art-df15af6c0222407f83ce8558b2e5a24e2023-11-19T12:39:29ZengBMCBMC Nephrology1471-23692023-08-0124111510.1186/s12882-023-03294-zGlomerular proteomic profiling reveals early differences between preexisting and de novo type 2 diabetes in human renal allograftsAnne Kipp0Hans-Peter Marti1Janka Babickova2Sigrid Nakken3Sabine Leh4Thea A. S. Halden5Trond Jenssen6Bjørn Egil Vikse7Anders Åsberg8Giulio Spagnoli9Jessica Furriol10Department of Clinical Medicine, University of BergenDepartment of Clinical Medicine, University of BergenDepartment of Clinical Medicine, University of BergenDepartment of Clinical Medicine, University of BergenDepartment of Clinical Medicine, University of BergenDepartment of Transplantation Medicine, Oslo University Hospital, Rikshospitalet and University of OsloDepartment of Transplantation Medicine, Oslo University Hospital, Rikshospitalet and University of OsloDepartment of Clinical Medicine, University of BergenDepartment of Transplantation Medicine, Oslo University Hospital, Rikshospitalet and University of OsloInstitute of Translational Pharmacology, National Research CouncilDepartment of Clinical Medicine, University of BergenAbstract Background Diabetes mellitus (DM), either preexisting or developing after transplantation, remains a crucial clinical problem in kidney transplantation. To obtain insights into the molecular mechanisms underlying PTDM development and early glomerular damage before the development of histologically visible diabetic kidney disease, we comparatively analysed the proteome of histologically normal glomeruli from patients with PTDM and normoglycaemic (NG) transplant recipients. Moreover, to assess specificities inherent in PTDM, we also comparatively evaluated glomerular proteomes from transplant recipients with preexisting type 2 DM (T2DM). Methods Protocol biopsies were obtained from adult NG, PTDM and T2DM patients one year after kidney transplantation. Biopsies were formalin-fixed and embedded in paraffin, and glomerular cross-sections were microdissected. A total of 4 NG, 7 PTDM and 6 T2DM kidney biopsies were used for the analysis. The proteome was determined by liquid chromatography-tandem mass spectrometry. Relative differences in protein abundance and significantly dysregulated pathways were analysed. Results Proteins involved in cell adhesion, immune response, leukocyte transendothelial filtration, and cell localization and organization were less abundant in glomeruli from PTDM patients than in those from NG patients, and proteins associated with supramolecular fibre organization and protein-containing complex binding were more abundant in PTDM patients. Overall, proteins related to adherens and tight junctions and those related to the immune system, including leukocyte transendothelial migration, were more abundant in NG patients than in transplanted patients with DM, irrespective of the timing of its development. However, proteins included in cell‒cell junctions and adhesion, insulin resistance, and vesicle-mediated transport were all less abundant in PTDM patients than in T2DM patients. Conclusions The glomerular proteome profile differentiates PTDM from NG and T2DM, suggesting specific pathogenetic mechanisms. Further studies are warranted to validate these results, potentially leading to an improved understanding of PTDM kidney transplant pathophysiology and to the identification of novel biomarkers.https://doi.org/10.1186/s12882-023-03294-zPTDMT2DMProteomicsTissue transplantationKidney |
| spellingShingle | Anne Kipp Hans-Peter Marti Janka Babickova Sigrid Nakken Sabine Leh Thea A. S. Halden Trond Jenssen Bjørn Egil Vikse Anders Åsberg Giulio Spagnoli Jessica Furriol Glomerular proteomic profiling reveals early differences between preexisting and de novo type 2 diabetes in human renal allografts BMC Nephrology PTDM T2DM Proteomics Tissue transplantation Kidney |
| title | Glomerular proteomic profiling reveals early differences between preexisting and de novo type 2 diabetes in human renal allografts |
| title_full | Glomerular proteomic profiling reveals early differences between preexisting and de novo type 2 diabetes in human renal allografts |
| title_fullStr | Glomerular proteomic profiling reveals early differences between preexisting and de novo type 2 diabetes in human renal allografts |
| title_full_unstemmed | Glomerular proteomic profiling reveals early differences between preexisting and de novo type 2 diabetes in human renal allografts |
| title_short | Glomerular proteomic profiling reveals early differences between preexisting and de novo type 2 diabetes in human renal allografts |
| title_sort | glomerular proteomic profiling reveals early differences between preexisting and de novo type 2 diabetes in human renal allografts |
| topic | PTDM T2DM Proteomics Tissue transplantation Kidney |
| url | https://doi.org/10.1186/s12882-023-03294-z |
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