RESUMEN
BACKGROUND: Mesenchymal stromal cells (MSCs) represent an option for the treatment of acute kidney injury (AKI). It is known that young stem cells are better than are aged stem cells at reducing the incidence of the senescent phenotype in the kidneys. The objective of this study was to determine whether AKI leads to premature, stress-induced senescence, as well as whether human umbilical cord-derived MSCs (huMSCs) can prevent ischaemia/reperfusion injury (IRI)-induced renal senescence in rats. METHODS: By clamping both renal arteries for 45 min, we induced IRI in male rats. Six hours later, some rats received 1 × 106 huMSCs or human adipose-derived MSCs (aMSCs) intraperitoneally. Rats were euthanised and studied on post-IRI days 2, 7 and 49. RESULTS: On post-IRI day 2, the kidneys of huMSC-treated rats showed improved glomerular filtration, better tubular function and higher expression of aquaporin 2, as well as less macrophage infiltration. Senescence-related proteins (ß-galactosidase, p21Waf1/Cip1, p16INK4a and transforming growth factor beta 1) and microRNAs (miR-29a and miR-34a) were overexpressed after IRI and subsequently downregulated by the treatment. The IRI-induced pro-oxidative state and reduction in Klotho expression were both reversed by the treatment. In comparison with huMSC treatment, the treatment with aMSCs improved renal function to a lesser degree, as well as resulting in a less pronounced increase in the renal expression of Klotho and manganese superoxide dismutase. Treatment with huMSCs ameliorated long-term kidney function after IRI, minimised renal fibrosis, decreased ß-galactosidase expression and increased the expression of Klotho. CONCLUSIONS: Our data demonstrate that huMSCs attenuate the inflammatory and oxidative stress responses occurring in AKI, as well as reducing the expression of senescence-related proteins and microRNAs. Our findings broaden perspectives for the treatment of AKI.
Asunto(s)
Lesión Renal Aguda/terapia , Sangre Fetal/metabolismo , Glucuronidasa/genética , Trasplante de Células Madre Mesenquimatosas , Células Madre Mesenquimatosas/metabolismo , Daño por Reperfusión/terapia , Lesión Renal Aguda/genética , Lesión Renal Aguda/metabolismo , Lesión Renal Aguda/patología , Tejido Adiposo/citología , Tejido Adiposo/metabolismo , Animales , Acuaporina 2/genética , Acuaporina 2/metabolismo , Inhibidor p16 de la Quinasa Dependiente de Ciclina/genética , Inhibidor p16 de la Quinasa Dependiente de Ciclina/metabolismo , Inhibidor p21 de las Quinasas Dependientes de la Ciclina/genética , Inhibidor p21 de las Quinasas Dependientes de la Ciclina/metabolismo , Sangre Fetal/citología , Regulación de la Expresión Génica , Tasa de Filtración Glomerular , Glucuronidasa/metabolismo , Humanos , Riñón/irrigación sanguínea , Riñón/metabolismo , Riñón/patología , Proteínas Klotho , Masculino , Células Madre Mesenquimatosas/citología , MicroARNs/genética , MicroARNs/metabolismo , Estrés Oxidativo , Ratas , Ratas Endogámicas WKY , Arteria Renal/lesiones , Daño por Reperfusión/genética , Daño por Reperfusión/metabolismo , Daño por Reperfusión/patología , Superóxido Dismutasa/genética , Superóxido Dismutasa/metabolismo , Factor de Crecimiento Transformador beta1/genética , Factor de Crecimiento Transformador beta1/metabolismo , Trasplante Heterólogo , beta-Galactosidasa/genética , beta-Galactosidasa/metabolismoRESUMEN
Estrogen has an important function in swine reproduction and growth. A Pvu II restriction enzyme polymorphism has been proven to be an important genetic variation in the estrogen receptor gene (ESR) and may be considered as a candidate gene for use in pig production but there is no data regarding the prevalence of this polymorphism in the Brazilian pig population. We used DNA samples from the following three purebred pig breeds: Large White (336 females and 26 males), Landrace (304 females and 27 males) and Pietrain (125 females and 11 males). The ESR genotyping was performed using PCR-RFLP. For each breed, genotypes for the ESR gene were compared independently for expected progeny differences (EPD) in litter size (LS), average daily weight gain (DWG) (g/day) and back fat thickness (BT) as measured in mm by ultrasound. In the Large White breed, but not the other breeds, the ESR genotype was significantly (p < 0.05) associated to LS, DWG and BT. Large Whites genotyped as AA or AB had higher EPD values for the LS and BT traits compared to BB Large Whites, while AA Large Whites had higher DWG EPD values than BB Large Whites. Our results for the Large White population showed that the A allele has a beneficial effect on LS, DWG and BT expected progeny differences.
Asunto(s)
Animales , Receptores de Estrógenos/genética , Porcinos/genética , Variación Genética , Polimorfismo Genético , Polimorfismo de Longitud del Fragmento de Restricción , ReproducciónRESUMEN
O aumento da produtividade e qualidade dos produtos animais vem se tornando de grande interesse econômico. A prolactina (PRL) é um hormônio essencial para o sucesso reprodutivo e seu receptor (RPRL) tem sido detectado em vários tecidos². O gene RPRL foi recentemente mapeado em suínos no cromossomo 16(6). Este trabalho teve como objetivo analisar a frequência genotípica do RPRL em três diferentes raças de suíno, Landrace, Large White e Pietrain e correlacionar os genótipos com características de interesse. Foram analisados um total de 124 animais. O DNA foi extraído de sangue total suíno e submetido a técnica de PCR-RFLP, para determinação do genótipo do gene do receptor da prolactina. As análises estatísticas mostraram que o genótipo RPRL teve efeito sobre peso médio diário na raça Landrace (p<0,0135). As médias de DEPGMD na raça Landrace também foram diferentes em relação ao genótipo (p< 0,0610), confirmando a análise dos dados reais de Ganho de Peso Médio Diário. Métodos de seleção assistida por marcadores, juntamente com métodos de seleção tradicional poderão ser utilizados para potencializar e acelerar o melhoramento de características de interesse econômico em suínos, onde o gene do receptor de prolactina (RPRL) poderá ser utilizado como um marcador molecular para o ganho de peso médio diário real e sua DEP.