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1.
Mol Cell Endocrinol ; 592: 112348, 2024 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-39218056

RESUMEN

The developmental origins of healthy and disease (DOHaD) concept has demonstrated a higher rate of chronic diseases in the adult population of individuals whose mothers experienced severe maternal protein restriction (MPR). Using proteomic and in silico analyses, we investigated the lung proteomic profile of young and aged rats exposed to MPR during pregnancy and lactation. Our results demonstrated that MPR lead to structural and immune system pathways changes, and this outcome is coupled with a rise in the PI3k-AKT-mTOR signaling pathway, with increased MMP-2 activity, and CD8 expression in the early life, with long-term effects with aging. This led to the identification of commonly or inversely differentially expressed targets in early life and aging, revealing dysregulated pathways related to the immune system, stress, muscle contraction, tight junctions, and hemostasis. We identified three miRNAs (miR-378a-3p, miR-378a-5p, let-7a-5p) that regulate four proteins (ACTN4, PPIA, HSPA5, CALM1) as probable epigenetic lung marks generated by MPR. In conclusion, MPR impacts the lungs early in life, increasing the possibility of long-lasting negative outcomes for respiratory disorders in the offspring.


Asunto(s)
Pulmón , MicroARNs , Proteómica , Animales , Femenino , Pulmón/metabolismo , Masculino , Proteómica/métodos , Embarazo , MicroARNs/genética , MicroARNs/metabolismo , Ratas , Efectos Tardíos de la Exposición Prenatal/metabolismo , Efectos Tardíos de la Exposición Prenatal/genética , Dieta con Restricción de Proteínas , Transducción de Señal , Serina-Treonina Quinasas TOR/metabolismo , Serina-Treonina Quinasas TOR/genética , Longevidad/genética , Ratas Wistar , Proteínas Proto-Oncogénicas c-akt/metabolismo , Proteoma/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Fosfatidilinositol 3-Quinasas/genética , Envejecimiento/metabolismo , Envejecimiento/genética , Metaloproteinasa 2 de la Matriz/metabolismo , Metaloproteinasa 2 de la Matriz/genética
2.
Mol Cell Endocrinol ; 588: 112223, 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38556160

RESUMEN

Maternal malnutrition can alter developmental biology, programming health and disease in offspring. The increase in sugar consumption during the peripubertal period, a worldwide concern, also affects health through adulthood. Studies have shown that maternal exposure to a low protein diet (LPD) is associated with an increase in prostate disease with aging. However, the combined effects of maternal LPD and early postnatal sugar consumption on offspring prostate disorders were not investigated. The effects on aging were evaluated using a maternal gestational model with lactational LPD (6% protein) and sugar consumption (10%) from postnatal day (PND) 21-90, associating the consequences on ventral prostate (VP) rats morphophysiology on PND540. An increase was shown in mast cells and in the VP of the CTR + SUG and Gestational and Lactational Low Protein (GLLP) groups. In GLLP + SUG, a significant increase was shown in TGF-ß1 expression in both the systemic and intra-prostatic forms, and SMAD2/3p had increased. The study identified maternal LPD and sugar consumption as risk factors for prostatic homeostasis in senility, activating the TGFß1-SMAD2/3 pathway, a signaling pathway with potential markers for prostatic disorders.


Asunto(s)
Desnutrición , Fenómenos Fisiologicos Nutricionales Maternos , Efectos Tardíos de la Exposición Prenatal , Próstata , Enfermedades de la Próstata , Animales , Masculino , Femenino , Embarazo , Efectos Tardíos de la Exposición Prenatal/metabolismo , Enfermedades de la Próstata/patología , Enfermedades de la Próstata/etiología , Enfermedades de la Próstata/metabolismo , Desnutrición/complicaciones , Próstata/metabolismo , Próstata/patología , Ratas , Inflamación/patología , Inflamación/metabolismo , Factor de Crecimiento Transformador beta1/metabolismo , Factor de Crecimiento Transformador beta1/genética , Dieta con Restricción de Proteínas/efectos adversos , Proteína Smad2/metabolismo , Ratas Wistar , Proteína smad3/metabolismo , Proteína smad3/genética , Transducción de Señal , Animales Recién Nacidos , Mastocitos/metabolismo
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