The molecular mechanisms of extracellular matrix-derived hydrogel therapy in idiopathic pulmonary fibrosis models

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dc.contributor(LETA) Lab. Toxinologia Aplicadapt_BR
dc.contributorPrograma de Pós-Graduação em Ciências – Toxinologia (PPGTox)pt_BR
dc.contributor.authorEvangelista-Leite, Danielept_BR
dc.contributor.authorCarreira, Ana C. O.pt_BR
dc.contributor.authorNishiyama Junior, Milton Yutakapt_BR
dc.contributor.authorGilpin, Sarah E.pt_BR
dc.contributor.authorMiglino, Maria A.pt_BR
dc.identifier.citationEvangelista-Leite D, Carreira AC.O., Nishiyama Junior MY, Gilpin SE., Miglino MA.. The molecular mechanisms of extracellular matrix-derived hydrogel therapy in idiopathic pulmonary fibrosis models. Biomaterials. 2023 Nov; 302:122338pt_BR
dc.description.abstractIdiopathic Pulmonary Fibrosis (IPF) is a progressively debilitating lung condition characterized by oxidative stress, cell phenotype shifts, and excessive extracellular matrix (ECM) deposition. Recent studies have shown promising results using decellularized ECM-derived hydrogels produced through pepsin digestion in various lung injury models and even a human clinical trial for myocardial infarction. This study aimed to characterize the composition of ECM-derived hydrogels, assess their potential to prevent fibrosis in bleomycin-induced IPF models, and unravel their underlying molecular mechanisms of action. Porcine lungs were decellularized and pepsin-digested for 48 h. The hydrogel production process, including visualization of protein molecular weight distribution and hydrogel gelation, was characterized. Peptidomics analysis of ECM-derived hydrogel contained peptides from 224 proteins. Probable bioactive and cell-penetrating peptides, including collagen IV, laminin beta 2, and actin alpha 1, were identified. ECM-derived hydrogel treatment was administered as an early intervention to prevent fibrosis advancement in rat models of bleomycin-induced pulmonary fibrosis. ECM-derived hydrogel concentrations of 1 mg/mL and 2 mg/mL showed subtle but noticeable effects on reducing lung inflammation, oxidative damage, and protein markers related to fibrosis (e.g., alpha-smooth muscle actin, collagen I). Moreover, distinct changes were observed in macroscopic appearance, alveolar structure, collagen deposition, and protein expression between lungs that received ECM-derived hydrogel and control fibrotic lungs. Proteomic analyses revealed significant protein and gene expression changes related to cellular processes, pathways, and components involved in tissue remodeling, inflammation, and cytoskeleton regulation. RNA sequencing highlighted differentially expressed genes associated with various cellular processes, such as tissue remodeling, hormone secretion, cell chemotaxis, and cytoskeleton engagement. This study suggests that ECM-derived hydrogel treatment influence pathways associated with tissue repair, inflammation regulation, cytoskeleton reorganization, and cellular response to injury, potentially offering therapeutic benefits in preventing or mitigating lung fibrosis.pt_BR
dc.description.sponsorship(CAPES) Coordenação de Aperfeiçoamento de Pessoal de Nível Superiorpt_BR
dc.description.sponsorship(CNPq) Conselho Nacional de Desenvolvimento Científico e Tecnológicopt_BR
dc.description.sponsorship(FAPESP) Fundação de Amparo à Pesquisa do Estado de São Paulopt_BR
dc.rightsRestricted accesspt_BR
dc.titleThe molecular mechanisms of extracellular matrix-derived hydrogel therapy in idiopathic pulmonary fibrosis modelspt_BR
dc.contributor.external(USP) Universidade de São Paulopt_BR
dc.contributor.external(UNICAMP) Universidade Estadual de Campinaspt_BR
dc.contributor.external(UFABC) Universidade Federal do ABCpt_BR
dc.subject.keyworddecellularized extracellular matrixpt_BR
dc.subject.keywordidiopathic pulmonary fibrosispt_BR
dc.identifier.citationabntv. 302, 122338, nov. 2023pt_BR
dc.identifier.citationvancouver2023 Nov; 302:122338pt_BR
dc.contributor.butantanNishiyama Junior, Milton Yutaka|:Pesquisador|:Docente PPGTox|:(LETA) Lab. Toxinologia Aplicada|:Programa de Pós-Graduação em Ciências – Toxinologia (PPGTox)pt_BR
dc.sponsorship.butantan(CAPES) Coordenação de Aperfeiçoamento de Pessoal de Nível Superior¦¦001pt_BR
dc.sponsorship.butantan(CNPq) Conselho Nacional de Desenvolvimento Científico e Tecnológico¦¦pt_BR
dc.sponsorship.butantan(FAPESP) Fundação de Amparo à Pesquisa do Estado de São Paulo¦¦14/50844-3pt_BR
dc.description.internalPolítica de depósito: liberado apenas preprintpt_BR
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