The growth factors present during liver regeneration partially overlap with the regulators of the hepatic acute phase response. We analysed the acute phase reaction and changes in soluble cytokine receptors after partial hepatectomy, when tissue injury inducing acute phase reaction and major reduction of liver mass occur simultaneously. Three acute phase proteins and mRNAs were determined by ELISA and northern blot hybridisation in rats. Serum levels of IL-6 and three soluble cytokine receptors (sTNF-alpha R I and II, sIL-6R) were detected by ELIBA or dot-blot assay. Time-course profiles of fibrinogen, alpha(2)-macroglobulin and haptoglobin proteins and mRNA are presented. Elevation of IL-6, soluble TNF-alpha receptors and soluble IL-6 receptor levels were also detected. The time-course of changes in haptoglobin concentration and elevation of soluble cytokine receptors is described by this in vivo experimental system. The results show good correlation with (post)transcriptional activation of immediate and delayed early gene products. These data suggest the involvement of both acute phase proteins and soluble cytokine receptors in the regulation of liver regeneration.
In rats within the first week of partial hepatectomy reconstruction of the normal histological structure of the liver already starts. To approach the possible role of endogenous glucocorticoids in the process of regeneration we measured the changes in the expression of steroid glucocorticoid receptor gene after various regeneration intervals. After partial hepatectomy, between 0.5 168 hours from the surgery, the gene expression (mRNA) of glucocorticoid receptor was determined by reverse transcription followed by PCR and normalized to that of glycerolphoshate dehydrogenase. Two peaks of glucocorticoid receptor mRNA were detected first, between 3 and 6 hours (first peak) and a second between 24 and 36 hours. Immunoreactive glucocorticoid receptor was detected by immunohistochemistry using monoclonal anti-glucocorticoid receptor. Three days after the surgery immunohistochemical studies showed substantially more immunoreactive GcR protein in the regenerated liver than in the controls. These semiquantitative data provide evidence suggesting elevation of glucocorticoid receptor expression during regeneration of liver at mRNA and protein levels.
Az epigenetikai mechanizmusok az alapvető életfolyamatok irányításában részt vevő gének működésére gyakorolnak hatást. E környezeti tényezők némelyike képes a génműködés megváltoztatására vagy kiiktatására. A környezet génaktivitásra gyakorolt, örökölhető fenotípus-változásokat eredményező hatásai a kromatinban úgynevezett epigenetikus jelzéseket hoznak létre, amelyek a DNS kémiai módosulását okozzák. A szülészet-nőgyógyászatban számos olyan terhespatológiai, onkológiai és nem daganatos nőgyógyászati kórkép van, amelyek kialakulásában az epigenetikai mechanizmusok fontos szerepet játszanak. A leiomyoma uteri számos etiológiai tényező együttállása esetén alakul ki, ezért hátterében egy feltehetően komplexebb epigenetikai szabályozórendszer jelenléte valószínűsíthető. Az endometriosis multifaktoriális kóreredete immunológiai és hormonális kóroki tényezők szerepét valószínűsíti. Ezek hatásmechanizmusának minél részletesebb génszintű ismerete jelent(ene) lehetőséget az érvényre jutó epigenetikai mechanizmusok azonosítására, illetve -a későbbiekben -hatásuk kiküszöbölésére. A polycystás ovarium szindróma vonatkozásában az epigenetikai kutatások irányát meghatározza a valószínűsíthető in utero eredet, amely mind a prekoncepcionális, mind a terhesgondozás során a megelőzés és a kezelés lehetőségeit kínálhatja. Orv. Hetil., 2014, 155(13), 492-499. Kulcsszavak: epigenetika, DNS-metiláció, endometriosis, PCOS, leiomyoma uteri, miRNS Epigenetic background of the most common non-oncologic gynecological diseasesEpigenetic effects infl uence the function of genes regulating the main physiological mechanisms. Some of these environmental factors may reduce or inhibit the function of these genes. The environmental effects on gene function may result in a change of the DNA structure leading to non-heritable phenotype changes. Epigenetic factors play an important etiological role in the development of numerous diseases in obstetrics and gynecology. Uterine fi broids probably have a complex etiological background including epigenetic mechanisms. The multifactorial aetiology of endometriosis suggests key roles for immunological and hormonal factors in the development of the diseases. These mechanisms are infl uenced by epigenetic factors, which may serve as therapeutic targets in the future. The possible in utero origin of polycystic ovary syndrome determines the main directions of research concerning epigenetic factors in the etiological background, with the hope of eventual prevention and/or treatment in the preconceptional period as well as during pregnancy care.
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