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1.
Physiol Rep ; 12(14): e16152, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-39054559

RESUMO

Plasma fibronectin (pFN) is a hepatocyte-derived circulating extracellular matrix protein that affects cell morphology, adipogenesis, and insulin signaling of adipocytes in vitro. In this study, we show pFN accrual to adipose tissue and its contribution to tissue homeostasis in mice. Hepatocyte-specific conditional Fn1 knockout mice (Fn1-/-ALB) show a decrease in adipose tissue FN levels and enhanced insulin sensitivity of subcutaneous (inguinal), visceral (epididymal) adipose tissue on a normal diet. Diet-induced obesity model of the Fn1-/-ALB mouse showed normal weight gain and whole-body fat mass, and normal adipose tissue depot volumes and unaltered circulating leptin and adiponectin levels. However, Fn1-/-ALB adipose depots showed significant alterations in adipocyte size and gene expression profiles. The inguinal adipose tissue on a normal diet, which had alterations in fatty acid metabolism and thermogenesis suggesting browning. The presence of increased beige adipocyte markers Ucp1 and Prdm16 supported this. In the inguinal fat, the obesogenic diet resulted in downregulation of the browning markers and changes in gene expression reflecting development, morphogenesis, and mesenchymal stem cell maintenance. Epididymal adipose tissue showed alterations in developmental and stem cell gene expression on both diets. The data suggests a role for pFN in adipose tissue insulin sensitivity and cell profiles.


Assuntos
Fibronectinas , Resistência à Insulina , Animais , Camundongos , Fibronectinas/metabolismo , Fibronectinas/genética , Masculino , Adipócitos/metabolismo , Tecido Adiposo/metabolismo , Adipogenia , Camundongos Knockout , Camundongos Endogâmicos C57BL , Obesidade/metabolismo , Obesidade/genética , Obesidade/sangue , Diferenciação Celular , Dieta Hiperlipídica
2.
Drug Deliv Transl Res ; 10(1): 108-121, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31428941

RESUMO

Bone tissue engineering aims to develop bone graft structure that can heal bone defects without using autografts or allografts. The current study was conducted to promote bone regeneration using a collagen type I hydrogel containing tacrolimus. For this purpose, different amounts of tacrolimus (10 µg/ml, 100 µg/ml, and 1000 µg/ml) were loaded into the hydrogel. The resulting drug-loaded hydrogels were characterized for their porosity, swelling capacity, weight loss, drug release, blood compatibility, and cell proliferation (MTT). For functional analysis, the developed hydrogel surrounded by a film made of gelatin and polycaprolactone (PCL) was administrated in the calvarias defect of Wistar rats. The results indicated that the hydrogel has a porosity of 89.2 ± 12.5% and an appropriate swelling, drug release, and blood compatibility behavior. The in vitro results indicated that the collagen hydrogel containing 1000 µg tacrolimus was adequate in terms of cell proliferation. Finally, in vivo studies provided some evidence of the potential of the developed hydrogel for bone healing.


Assuntos
Colágeno Tipo I/química , Consolidação da Fratura/efeitos dos fármacos , Crânio/lesões , Tacrolimo/administração & dosagem , Engenharia Tecidual/métodos , Animais , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Modelos Animais de Doenças , Humanos , Hidrogéis , Masculino , Porosidade , Ratos , Ratos Wistar , Crânio/efeitos dos fármacos , Tacrolimo/química , Tacrolimo/farmacologia , Alicerces Teciduais
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