Browsing by Subject "intestine"
Now showing items 1-4 of 4
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(2019)Reniini-angiotensiinijärjestelmän (RAS) paikallisia toimintoja on kuvattu monissa kudoksissa. RAS:n fysiologinen kokonaisvaikutus on riippuvainen kahden vastavaikuttavan biokemiallisen akselin suhteellisesta aktiivisuudesta. Klassisen akselin muodostavat angiotensiinikonvertaasi (ACE), angiotensiini II (Ang II) ja tyypin 1 angiotensiini II -reseptori (AT1R). Vaihtoehtoiseen akseliin kuuluvat angiotensiinikonvertaasi 2 [ACE2], angiotensiini 1-7 [Ang (1-7)] sekä Mas-reseptori (MAS). Suoliston paikallinen RAS toimii parakriinisena säätelijänä ja osallistuu tulehduksen säätelyyn. Järjestelmän vaikutus paikalliseen kudokseen riippuu klassisen ja vaihtoehtoisen akselin aktiivisuuksien suhteesta. Klassinen akseli edistää ja vaihtoehtoinen akseli lievittää tulehdusta. Paikallisten reniini- angiotensiinijärjestelmien toiminnan ja akselien välisen suhteen tiedetään muuttuvan ikääntyessä. Asiaa ei kuitenkaan aiemmin ole tutkittu suoliston osalta. Tutkimukseni kartoitti paikallisen RAS:n ilmentymistä nuorten ja vanhojen rottien suolistossa. Tutkin jejunumia ja paksusuolta. Päälöydökseni oli, että vanhempien rottien suolistossa ACE:n ja ACE2:n suhde oli korkeampi, sekä entsyymiaktiivisuudella että proteiinikonsentraatiolla mitattuna. Näyttää siltä, että ikääntymisen myötä rottien suoliston paikallisen reniini-angiotensiinijärjestelmän toiminta painottuu klassiselle ACE-välitteiselle akselille. On mahdollista, että paikallisen RAS:n toiminnan painottuminen ACE-välitteiselle akselille liittyy siihen, että iän myötä suolistossa tapahtuu tulehduksen ja sidekudoksen muodostuksen lisääntymistä.
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(2023)Intestinal epithelium is capable of rapid regeneration, which is associated with transient changes in cellular identity. Some of these changes involve an enrichment of fetal-like gene expression and simultaneous suppression of adult stem cell signature. Interestingly, the upregulation of fetal-like marker Stem cell antigen 1 (Sca1) is modulated by extracellular matrix (ECM) which is known to guide epithelial cells during regeneration. Our recently published decellularized small intestinal ECM (iECM) system retains the composition and topology of natural ECM. This makes it an attractive system for ex vivo studies addressing regeneration. This thesis aimed to gain insight into the fetal-like identity and its dynamics using an ex vivo iECM system. Intriguingly, Sca1 expressing cells on iECM displayed migratory features, such as a leading edge and changes in nuclear morphology. Curiously, these features are typical for epithelial cells during development. Furthermore, based on marker gene expression during iECM re-epithelization, fetal-like state was upregulated while adult stem cell state was downregulated, revealing a gradually emerging inverse correlation. Additionally, data suggests that circadian rhythms may have a role in modulating the fetal-like state. iECM from an active-state mice indicated a reduced capability to induce fetal-like identity and overall re-epithelization compared to the rest-state iECM. The results of this thesis suggest further potential of iECM system in studying emergence of fetal-like state during re-epithelization and circadian rhythm impact on it.
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(2023)Intestinal epithelium is capable of rapid regeneration, which is associated with transient changes in cellular identity. Some of these changes involve an enrichment of fetal-like gene expression and simultaneous suppression of adult stem cell signature. Interestingly, the upregulation of fetal-like marker Stem cell antigen 1 (Sca1) is modulated by extracellular matrix (ECM) which is known to guide epithelial cells during regeneration. Our recently published decellularized small intestinal ECM (iECM) system retains the composition and topology of natural ECM. This makes it an attractive system for ex vivo studies addressing regeneration. This thesis aimed to gain insight into the fetal-like identity and its dynamics using an ex vivo iECM system. Intriguingly, Sca1 expressing cells on iECM displayed migratory features, such as a leading edge and changes in nuclear morphology. Curiously, these features are typical for epithelial cells during development. Furthermore, based on marker gene expression during iECM re-epithelization, fetal-like state was upregulated while adult stem cell state was downregulated, revealing a gradually emerging inverse correlation. Additionally, data suggests that circadian rhythms may have a role in modulating the fetal-like state. iECM from an active-state mice indicated a reduced capability to induce fetal-like identity and overall re-epithelization compared to the rest-state iECM. The results of this thesis suggest further potential of iECM system in studying emergence of fetal-like state during re-epithelization and circadian rhythm impact on it.
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(2020)High blood pressure has been shown to increase intestinal permeability, which is associated with several diseases such as inflammatory bowel diseases (IBD) and irritable bowel syndrome (IBS). Recently, renin-angiotensin system (RAS) components, the main regulators of blood pressure, have been found to be produced also locally in several tissues e.g. intestine, heart and brain. In the intestine, the local RAS participates in the regulation of inflammation. However, little is known of the functionality of the local intestinal RAS components and their involvement in the regulation of the intestinal barrier function. Conventional angiotensin-converting enzyme (ACE)-angiotensin receptor type 1 (AT1R) axis and the alternative angiotensin-converting enzyme 2 (ACE2)- Mas receptor axis have opposing functions in the body. The disbalance between the two pathways has been associated with different pathophysiological processes. This in vitro study aimed to assess the direct effect of proinflammatory angiotensin II (Ang II) via the activation of AT1R on intestinal permeability of 8-10-week-old Balb/c mice. Jejunum and colon samples were collected and mounted to the Ussing chamber with different Ang II concentrations or a combination of Ang II and AT1R antagonist losartan. Angiotensin (1-7) (Ang (1-7)), a Mas receptor agonist, was also examined for its possible beneficial effect on reducing gut permeability and on alleviating the harmful effects of Ang II. Transepithelial resistance (TER) and short-circuit current (Isc) were analyzed as indicators of the permeability. Given the importance of the tight junction proteins to paracellular permeability, the levels of occludin, claudin-1 and claudin-4 were determined with Western blot from jejunum and colon samples incubated for 75 min under similar conditions used in the Ussing chamber. Ang II increased the paracellular permeability via the activation of AT1R in jejunum. Additionally, Ang (1-7) tended to alleviate the negative effects of Ang II. Changes in tight junction protein levels partly were in accordance with the permeability findings. The fluorescence permeability marker (9Å) used mimics the size of disaccharides. There is evidence that TER measures the changes in the paracellular ion and water transport and as no alterations in TER values were observed we suggest that Ang II increases the flux of macromolecules via the activation of AT1R in jejunum. No significant changes in permeability or in the electrophysiological values were observed in colon after incubation with peptides.
Now showing items 1-4 of 4