Mice with Type 2 Diabetes Present Significant Alterations in Their Tissue Biomechanical Properties and Histological Features
Type 2 diabetes mellitus (T2DM) is a complex metabolic disease often associated with severe complications that may result in patient morbidity or death. One T2DM etiological agent is chronic hyperglycemia, a condition that induces damaging biological processes, including impactful extracellular matr...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2021-12-01
|
| Series: | Biomedicines |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2227-9059/10/1/57 |
| _version_ | 1827666566417743872 |
|---|---|
| author | Tânia B. Cruz Filomena A. Carvalho Paulo N. Matafome Raquel A. Soares Nuno C. Santos Rui D. Travasso Maria J. Oliveira |
| author_facet | Tânia B. Cruz Filomena A. Carvalho Paulo N. Matafome Raquel A. Soares Nuno C. Santos Rui D. Travasso Maria J. Oliveira |
| author_sort | Tânia B. Cruz |
| collection | DOAJ |
| description | Type 2 diabetes mellitus (T2DM) is a complex metabolic disease often associated with severe complications that may result in patient morbidity or death. One T2DM etiological agent is chronic hyperglycemia, a condition that induces damaging biological processes, including impactful extracellular matrix (ECM) modifications, such as matrix components accumulation. The latter alters ECM stiffness, triggering fibrosis, inflammation, and pathological angiogenesis. Hence, studying ECM biochemistry and biomechanics in the context of T2DM, or obesity, is highly relevant. With this in mind, we examined both native and decellularized tissues of obese B6.Cg-Lep<sup>ob</sup>/J (ob/ob) and diabetic BKS.Cg-Dock7m+/+Lepr<sup>db</sup>J (db/db) mice models, and extensively investigated their histological and biomechanical properties. The tissues analyzed herein were those strongly affected by diabetes—skin, kidney, adipose tissue, liver, and heart. The referred organs and tissues were collected from 8-week-old animals and submitted to classical histological staining, immunofluorescence, scanning electron microscopy, rheology, and atomic force microscopy. Altogether, this systematic characterization has identified significant differences in the architecture of both ob/ob and db/db tissues, namely db/db skin presents loose epidermis and altered dermis structure, the kidneys have clear glomerulopathy traits, and the liver exhibits severe steatosis. The distribution of ECM proteins also pinpoints important differences, such as laminin accumulation in db/db kidneys and decreased hyaluronic acid in hepatocyte cytoplasm in both obese and diabetic mice. In addition, we gathered a significant set of data showing that ECM features are maintained after decellularization, making these matrices excellent biomimetic scaffolds for 3D in vitro approaches. Importantly, mechanical studies revealed striking differences between tissue ECM stiffness of control (C57BL/6J), obese, and diabetic mice. Notably, we have unveiled that the intraperitoneal adipose tissue of diabetic animals is significantly stiffer (G* ≈ 10,000 Pa) than that of ob/ob or C57BL/6J mice (G* ≈ 3000–5000 Pa). Importantly, this study demonstrates that diabetes and obesity selectively potentiate severe histological and biomechanical alterations in different matrices that may impact vital processes, such as angiogenesis, wound healing, and inflammation. |
| first_indexed | 2024-03-10T01:52:27Z |
| format | Article |
| id | doaj.art-eeca8da73b9b489b9f3786759a691674 |
| institution | Directory Open Access Journal |
| issn | 2227-9059 |
| language | English |
| last_indexed | 2024-03-10T01:52:27Z |
| publishDate | 2021-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomedicines |
| spelling | doaj.art-eeca8da73b9b489b9f3786759a6916742023-11-23T13:03:04ZengMDPI AGBiomedicines2227-90592021-12-011015710.3390/biomedicines10010057Mice with Type 2 Diabetes Present Significant Alterations in Their Tissue Biomechanical Properties and Histological FeaturesTânia B. Cruz0Filomena A. Carvalho1Paulo N. Matafome2Raquel A. Soares3Nuno C. Santos4Rui D. Travasso5Maria J. Oliveira6i3S, Institute for Research and Innovation in Health, University of Porto, Rua Alfredo Allen, 4200-135 Porto, PortugalInstituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Avenida Prof. Egas Moniz, 1649-028 Lisbon, PortugaliCBR, Coimbra Institute for Clinical and Biomedical Research, Faculty of Medicine, University of Coimbra, Azinhaga Santa Comba, 3000-548 Coimbra, Portugali3S, Institute for Research and Innovation in Health, University of Porto, Rua Alfredo Allen, 4200-135 Porto, PortugalInstituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Avenida Prof. Egas Moniz, 1649-028 Lisbon, PortugalCFisUC, Centre for Physics of the University of Coimbra, Department of Physics, Rua Larga, 3004-516 Coimbra, Portugali3S, Institute for Research and Innovation in Health, University of Porto, Rua Alfredo Allen, 4200-135 Porto, PortugalType 2 diabetes mellitus (T2DM) is a complex metabolic disease often associated with severe complications that may result in patient morbidity or death. One T2DM etiological agent is chronic hyperglycemia, a condition that induces damaging biological processes, including impactful extracellular matrix (ECM) modifications, such as matrix components accumulation. The latter alters ECM stiffness, triggering fibrosis, inflammation, and pathological angiogenesis. Hence, studying ECM biochemistry and biomechanics in the context of T2DM, or obesity, is highly relevant. With this in mind, we examined both native and decellularized tissues of obese B6.Cg-Lep<sup>ob</sup>/J (ob/ob) and diabetic BKS.Cg-Dock7m+/+Lepr<sup>db</sup>J (db/db) mice models, and extensively investigated their histological and biomechanical properties. The tissues analyzed herein were those strongly affected by diabetes—skin, kidney, adipose tissue, liver, and heart. The referred organs and tissues were collected from 8-week-old animals and submitted to classical histological staining, immunofluorescence, scanning electron microscopy, rheology, and atomic force microscopy. Altogether, this systematic characterization has identified significant differences in the architecture of both ob/ob and db/db tissues, namely db/db skin presents loose epidermis and altered dermis structure, the kidneys have clear glomerulopathy traits, and the liver exhibits severe steatosis. The distribution of ECM proteins also pinpoints important differences, such as laminin accumulation in db/db kidneys and decreased hyaluronic acid in hepatocyte cytoplasm in both obese and diabetic mice. In addition, we gathered a significant set of data showing that ECM features are maintained after decellularization, making these matrices excellent biomimetic scaffolds for 3D in vitro approaches. Importantly, mechanical studies revealed striking differences between tissue ECM stiffness of control (C57BL/6J), obese, and diabetic mice. Notably, we have unveiled that the intraperitoneal adipose tissue of diabetic animals is significantly stiffer (G* ≈ 10,000 Pa) than that of ob/ob or C57BL/6J mice (G* ≈ 3000–5000 Pa). Importantly, this study demonstrates that diabetes and obesity selectively potentiate severe histological and biomechanical alterations in different matrices that may impact vital processes, such as angiogenesis, wound healing, and inflammation.https://www.mdpi.com/2227-9059/10/1/57extracellular matrix biomechanical propertiestissue decellularizationECM component distributiondiabetes-associated ECM modifications |
| spellingShingle | Tânia B. Cruz Filomena A. Carvalho Paulo N. Matafome Raquel A. Soares Nuno C. Santos Rui D. Travasso Maria J. Oliveira Mice with Type 2 Diabetes Present Significant Alterations in Their Tissue Biomechanical Properties and Histological Features Biomedicines extracellular matrix biomechanical properties tissue decellularization ECM component distribution diabetes-associated ECM modifications |
| title | Mice with Type 2 Diabetes Present Significant Alterations in Their Tissue Biomechanical Properties and Histological Features |
| title_full | Mice with Type 2 Diabetes Present Significant Alterations in Their Tissue Biomechanical Properties and Histological Features |
| title_fullStr | Mice with Type 2 Diabetes Present Significant Alterations in Their Tissue Biomechanical Properties and Histological Features |
| title_full_unstemmed | Mice with Type 2 Diabetes Present Significant Alterations in Their Tissue Biomechanical Properties and Histological Features |
| title_short | Mice with Type 2 Diabetes Present Significant Alterations in Their Tissue Biomechanical Properties and Histological Features |
| title_sort | mice with type 2 diabetes present significant alterations in their tissue biomechanical properties and histological features |
| topic | extracellular matrix biomechanical properties tissue decellularization ECM component distribution diabetes-associated ECM modifications |
| url | https://www.mdpi.com/2227-9059/10/1/57 |
| work_keys_str_mv | AT taniabcruz micewithtype2diabetespresentsignificantalterationsintheirtissuebiomechanicalpropertiesandhistologicalfeatures AT filomenaacarvalho micewithtype2diabetespresentsignificantalterationsintheirtissuebiomechanicalpropertiesandhistologicalfeatures AT paulonmatafome micewithtype2diabetespresentsignificantalterationsintheirtissuebiomechanicalpropertiesandhistologicalfeatures AT raquelasoares micewithtype2diabetespresentsignificantalterationsintheirtissuebiomechanicalpropertiesandhistologicalfeatures AT nunocsantos micewithtype2diabetespresentsignificantalterationsintheirtissuebiomechanicalpropertiesandhistologicalfeatures AT ruidtravasso micewithtype2diabetespresentsignificantalterationsintheirtissuebiomechanicalpropertiesandhistologicalfeatures AT mariajoliveira micewithtype2diabetespresentsignificantalterationsintheirtissuebiomechanicalpropertiesandhistologicalfeatures |