PMID- 35052737 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20220128 IS - 2227-9059 (Print) IS - 2227-9059 (Electronic) IS - 2227-9059 (Linking) VI - 10 IP - 1 DP - 2021 Dec 28 TI - Mice with Type 2 Diabetes Present Significant Alterations in Their Tissue Biomechanical Properties and Histological Features. LID - 10.3390/biomedicines10010057 [doi] LID - 57 AB - 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(ob)/J (ob/ob) and diabetic BKS.Cg-Dock7m+/+Lepr(db)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* approximately 10,000 Pa) than that of ob/ob or C57BL/6J mice (G* approximately 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. FAU - Cruz, Tania B AU - Cruz TB AD - i3S, Institute for Research and Innovation in Health, University of Porto, Rua Alfredo Allen, 4200-135 Porto, Portugal. AD - INEB, National Institute of Biomedical Engineering, Rua Alfredo Allen, 4200-135 Porto, Portugal. FAU - Carvalho, Filomena A AU - Carvalho FA AUID- ORCID: 0000-0001-6088-3894 AD - Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Avenida Prof. Egas Moniz, 1649-028 Lisbon, Portugal. FAU - Matafome, Paulo N AU - Matafome PN AUID- ORCID: 0000-0002-3422-290X AD - iCBR, Coimbra Institute for Clinical and Biomedical Research, Faculty of Medicine, University of Coimbra, Azinhaga Santa Comba, 3000-548 Coimbra, Portugal. AD - CIBB, Center for Innovative Biomedicine and Biotechnology, University of Coimbra, Rua Larga, 3004-516 Coimbra, Portugal. AD - CACC, Clinical-Academic Center of Coimbra, Faculty of Medicine, University of Coimbra, Rua Larga, 3004-516 Coimbra, Portugal. FAU - Soares, Raquel A AU - Soares RA AUID- ORCID: 0000-0002-9157-5541 AD - i3S, Institute for Research and Innovation in Health, University of Porto, Rua Alfredo Allen, 4200-135 Porto, Portugal. AD - Department of Biomedicine, Faculty of Medicine, University of Porto, Alameda Prof. Hernani Monteiro, 4200-319 Porto, Portugal. FAU - Santos, Nuno C AU - Santos NC AUID- ORCID: 0000-0002-0580-0475 AD - Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Avenida Prof. Egas Moniz, 1649-028 Lisbon, Portugal. FAU - Travasso, Rui D AU - Travasso RD AUID- ORCID: 0000-0001-6078-0721 AD - CFisUC, Centre for Physics of the University of Coimbra, Department of Physics, Rua Larga, 3004-516 Coimbra, Portugal. FAU - Oliveira, Maria J AU - Oliveira MJ AUID- ORCID: 0000-0002-0724-0272 AD - i3S, Institute for Research and Innovation in Health, University of Porto, Rua Alfredo Allen, 4200-135 Porto, Portugal. AD - INEB, National Institute of Biomedical Engineering, Rua Alfredo Allen, 4200-135 Porto, Portugal. AD - ICBAS, Institute of Biomedical Sciences Abel Salazar, University of Porto, Rua Jorge de Viterbo Ferreira, 4050-313 Porto, Portugal. LA - eng PT - Journal Article DEP - 20211228 PL - Switzerland TA - Biomedicines JT - Biomedicines JID - 101691304 PMC - PMC8773308 OTO - NOTNLM OT - ECM component distribution OT - diabetes-associated ECM modifications OT - extracellular matrix biomechanical properties OT - tissue decellularization COIS- The authors declare no conflict of interest. EDAT- 2022/01/22 06:00 MHDA- 2022/01/22 06:01 PMCR- 2021/12/28 CRDT- 2022/01/21 01:03 PHST- 2021/12/08 00:00 [received] PHST- 2021/12/22 00:00 [revised] PHST- 2021/12/23 00:00 [accepted] PHST- 2022/01/21 01:03 [entrez] PHST- 2022/01/22 06:00 [pubmed] PHST- 2022/01/22 06:01 [medline] PHST- 2021/12/28 00:00 [pmc-release] AID - biomedicines10010057 [pii] AID - biomedicines-10-00057 [pii] AID - 10.3390/biomedicines10010057 [doi] PST - epublish SO - Biomedicines. 2021 Dec 28;10(1):57. doi: 10.3390/biomedicines10010057.