Colonocyte Keratins are upregulated in hypoxia and affects nuclear translocation of HIF-1a
Ghimire, Aruna (2019)
Ghimire, Aruna
Åbo Akademi
2019
Julkaisu on tekijänoikeussäännösten alainen. Teosta voi lukea ja tulostaa henkilökohtaista käyttöä varten. Käyttö kaupallisiin tarkoituksiin on kielletty.
Julkaisun pysyvä osoite on
https://urn.fi/URN:NBN:fi-fe2019042513219
https://urn.fi/URN:NBN:fi-fe2019042513219
Tiivistelmä
The cytoskeleton is divided into three types: microtubules, microfilaments and intermediate filaments (IFs). IFs are further divided into 6 different types. First two types of IFs are type I and type II keratins. Keratins provide mechanical and non-mechanical strength to epithelial cells and they also protect cells from various types of stress. Both type I keratins (K18, K19 and K20) and type II keratins (K7 and K8) are present in colon. Keratins such as K7 and K20 are up-regulated under intestinal stress. During hypoxia (inadequate supply of oxygen (O2) to the cells), colonic epithelium expresses a transcriptional factor, hypoxia inducible factor- 1 alpha (HIF-1a). Hypoxia inducible factor-2a (HIF-2a) is also a transcriptional factor expressed in colon and has regenerative function. The hypothesis of this study was that the cells react to hypoxia by up-regulation of keratins, similar to stress. It was also hypothesized that keratins modulate hypoxia signaling pathway in colon. To understand how keratins and hypoxia signaling pathway are regulated, protein analysis, immunofluorescent staining, confocal imaging and image analysis were performed. From this study, it is found out that HIF-1a and HIF-2a are down-regulated in absence of K8 in basal colon of mice. In addition, K19 and K20 are up-regulated in hypoxic condition in mouse colon and colon cancer cells. Moreover, in vitro hypoxia study of the CRISPR/Cas9 Caco-2 cell showed up-regulation of HIF-1a more in K8-/- cells compared to K8+/+ cells. Similarly, HIF-1a translocate to nucleus more in K8-/- compared to K8+/+ cells. In conclusion, keratins are up-regulated in hypoxia and keratins regulate HIF signaling pathway.
Kokoelmat
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