Please use this identifier to cite or link to this item: https://hdl.handle.net/10316/103193
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dc.contributor.authorCruz, Tânia B.-
dc.contributor.authorCarvalho, Filomena A.-
dc.contributor.authorMatafome, Paulo N.-
dc.contributor.authorSoares, Raquel A-
dc.contributor.authorSantos, Nuno C.-
dc.contributor.authorTravasso, Rui D.-
dc.contributor.authorOliveira, Maria J.-
dc.date.accessioned2022-10-20T10:56:28Z-
dc.date.available2022-10-20T10:56:28Z-
dc.date.issued2021-12-28-
dc.identifier.issn2227-9059-
dc.identifier.urihttps://hdl.handle.net/10316/103193-
dc.description.abstractType 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-Lepob/J (ob/ob) and diabetic BKS.Cg-Dock7m+/+LeprdbJ (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.pt
dc.description.sponsorshipThis work was funded by FEDER funds through the Operational Programme Competitiveness Factors–COMPETE and by Fundação para a Ciência e a Tecnologia–Ministério da Ciência, Tecnologia e Ensino Superior (FCT-MCTES, Portugal) under the project “AngioDia- Modeling Angiogenesis in Type 2 Diabetes Mellitus-integrating experimental and theoretical approaches” POCI-01-0145- FEDER-031743–PTDC/BIA-CEL/31743/2017 (T.B.C., P.N.M., R.A.S., R.D.T., M.J.O.) and PTDC/EMDTLM/ 7289/2020 (N.C.S., F.A.C., R.D.T.), and under the strategic projects UIDB/04564/2020 (R.D.T.), UIDP/04564/2020 (R.D.T.), UIDB/04293/2020 (M.J.O.), and UID/BIM/50005/2020 (F.A.C., N.C.S.)-
dc.language.isoengpt
dc.rightsopenAccesspt
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/pt
dc.subjectextracellular matrix biomechanical propertiespt
dc.subjecttissue decellularizationpt
dc.subjectECM component distributionpt
dc.subjectdiabetes-associated ECM modificationspt
dc.titleMice with Type 2 Diabetes Present Significant Alterations in Their Tissue Biomechanical Properties and Histological Featurespt
dc.typearticlept
degois.publication.firstPage57pt
degois.publication.issue1pt
degois.publication.titleBiomedicinespt
dc.peerreviewedyespt
dc.identifier.doi10.3390/biomedicines10010057-
degois.publication.volume10pt
dc.date.embargo2021-12-28*
dc.identifier.pmid35052737-
uc.date.periodoEmbargo0pt
item.grantfulltextopen-
item.openairecristypehttp://purl.org/coar/resource_type/c_18cf-
item.fulltextCom Texto completo-
item.openairetypearticle-
item.cerifentitytypePublications-
item.languageiso639-1en-
crisitem.author.researchunitCNC - Center for Neuroscience and Cell Biology-
crisitem.author.orcid0000-0002-3422-290X-
crisitem.author.orcid0000-0001-6078-0721-
Appears in Collections:I&D ICBR - Artigos em Revistas Internacionais
I&D CIBB - Artigos em Revistas Internacionais
I&D CFis - Artigos em Revistas Internacionais
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