RESUMEN
We studied the intensity of age-specific changes in the dermis (number and proliferative activity of fibroblasts) in mice with normal and experimentally changed level of thyroid hormones. Receptors of thyroid hormones, TR-α and TR-ß, in mouse dermal fibroblasts were identified by immunohistochemical methods. The relative expression of Thra, Thrb, and Dio2 genes was assessed by real-time PCR analysis. From the second to fifth month of life, the number of fibroblasts in the connective tissue layer of mouse skin decreased by 42.3%. The number of fibroblasts in the dermis of 5-month-old mice treated with Thyrozol significantly decreases by 25.9% (p<0.05), and vice versa, in mice receiving thyroxin this parameter increased by 4.7% in comparison with the control (p>0.05). TR-α and TR-ß were identified in dermal fibroblasts in all groups of mice. No differences in the content TR-α and Thra gene expression in 2- and 5-month-old mice of the control and experimental were revealed. TR-ß content in dermal fibroblasts of 2-month-old animals was maximum and exceeded this value in 5-month-old control mice by 25%. The number of these receptors decreased by 33.3% in mice treated with Thyrozol and increased by 25% in animals receiving thyroxin injection in comparison with the control. Relative expression of Thrb gene significantly increased only in mice treated with thyroxin. Comparative analysis of the relative expression of Dio2 gene revealed no differences between the experimental and control groups. Changes in the level of thyroid hormones, content of TR-ß, and relative Thrb gene expression contribute to agerelated shifts in the number and proliferative activity of mouse dermal fibroblasts.
Asunto(s)
Envejecimiento/genética , Fibroblastos/metabolismo , Yoduro Peroxidasa/genética , Glándula Tiroides/metabolismo , Receptores alfa de Hormona Tiroidea/genética , Receptores beta de Hormona Tiroidea/genética , Envejecimiento/metabolismo , Animales , Antitiroideos/farmacología , Proliferación Celular , Dermis/citología , Dermis/efectos de los fármacos , Dermis/metabolismo , Fibroblastos/citología , Fibroblastos/efectos de los fármacos , Expresión Génica , Yoduro Peroxidasa/metabolismo , Antígeno Ki-67/genética , Antígeno Ki-67/metabolismo , Metimazol/farmacología , Ratones , Ratones Endogámicos , Glándula Tiroides/citología , Glándula Tiroides/efectos de los fármacos , Receptores alfa de Hormona Tiroidea/metabolismo , Receptores beta de Hormona Tiroidea/metabolismo , Tiroxina/farmacología , Yodotironina Deyodinasa Tipo IIRESUMEN
The goal of our work was to examine the effects of metformin on age-related changes in the number and proliferation of dermal fibroblasts in mice. The study of the dermis was carried out at five months' mice that received drinking water with metformin at concentrations 500 mg/l from two months (within 90 days). Five months' mice received drinking water without metformin and they were as a control. Material of two months' mice was also used in the work. We counted the total number of dermal fibroblasts and lobe of fibroblasts with positive coloration on Ki-67. The results showed that there has been a decrease in the total number of dermal fibroblasts by 42,3% from two months of mouse's life up to five months and lobe of fibroblasts with positive coloration on Ki-67 by 12%. The total number of dermal fibroblasts in five months' mice was lower for 13,4%by using metformin. The lobe of fibroblasts with positive coloration on Ki-67 was reduced by 27,3% in comparison with information of animals that have not received metformin. Thus, age-related reduction of dermal fibroblasts in mice is due to decline in their proliferative activity. Metformin has an inhibited impact on proliferation of dermal fibroblasts in mice.