| 1. |
- Meisgen, Florian, et al.
(författare)
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MiR-21 is up-regulated in psoriasis and suppresses T cell apoptosis.
- 2012
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Ingår i: Experimental dermatology. - : Wiley. - 0906-6705 .- 1600-0625. ; 21:4, s. 312-4
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Tidskriftsartikel (refereegranskat)abstract
- MicroRNAs are short non-coding RNAs that regulate gene expression. Previously, in a genome-wide screen, we found deregulation of microRNA expression in psoriasis skin. MicroRNA-21 (miR-21) is one of the microRNAs significantly up-regulated in psoriasis skin lesions. To identify the cell type responsible for the increased miR-21 level, we compared expression of miR-21 in epidermal cells and dermal T cells between psoriasis and healthy skin and found elevated levels of miR-21 in psoriasis in both cell types. In cultured T cells, expression of miR-21 increased markedly upon activation. To explore the function of miR-21 in primary human T helper cells, we inhibited miR-21 using a tiny seed-targeting LNA-anti-miR. Specific inhibition of miR-21 increased the apoptosis rate of activated T cells. Our results suggest that miR-21 suppresses apoptosis in activated T cells, and thus, overexpression of miR-21 may contribute to T cell-derived psoriatic skin inflammation.
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| 2. |
- Obad, Susanna, et al.
(författare)
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Expression of the IFN-inducible p53-target gene TRIM22 is down-regulated during erythroid differentiation of human bone marrow.
- 2007
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Ingår i: Leukemia Research: A Forum for Studies on Leukemia and Normal Hemopoiesis. - : Elsevier BV. - 1873-5835. ; 31:7, s. 995-1001
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Tidskriftsartikel (refereegranskat)abstract
- The interferon inducible protein TRIM22 has been identified as a p53 target gene, with possible involvement in proliferation and differentiation of leukaemia cells. Here, the expression levels of TRIM22 during haematopoietic differentiation are characterised. Expression of TRIM22 correlates inversely to differentiation, as TRIM22 is highly expressed in CD34(+) human bone marrow progenitor cells, but declines in mature populations. The erythroid lineage appears as a special case, as TRIM22 expression shows an extreme decrease during late erythroid maturation and is completely undetectable in nucleated erythroid populations in contrast to other lineages. In conclusion, our data Could suggest lineage-specific roles for TRIM22 during haematopoietic differentiation.
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| 3. |
- Obad, Susanna, et al.
(författare)
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Regulation of the interferon-inducible p53 target gene TRIM22 (Staf50) in human T lymphocyte activation
- 2007
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Ingår i: Journal of Interferon and Cytokine Research. - : Mary Ann Liebert Inc. - 1079-9907 .- 1557-7465. ; 27:10, s. 857-864
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Tidskriftsartikel (refereegranskat)abstract
- TRIM22 (Staf50) is an interferon (IFN)-inducible protein with unknown function. Recently, we identified TRIM22 as a novel p53 target gene and showed that overexpression of TRIM22 inhibits the clonogenic growth of monoblastic U937 cells. Moreover, expression of TRIM22 is high in lymphoid tissue, and levels decrease during T lymphocyte activation with CD3/CD2/CD28, suggesting that TRIM22 could exert antiproliferative effects. Here, a prominent increase in TRIM22 levels is observed during activation with interleukin-2 (IL-2) or IL-15 in contrast to the decrease observed during CD3/CD2/CD28-induced activation. However, stimulation of cells in these experiments was performed on crude T lymphocytes, allowing indirect regulation between different lymphocyte subtypes to take place. Therefore, to prevent interaction between different lymphocyte subtypes, expression of TRIM22 was examined during activation of sorted T lymphocyte subpopulations. In contrast to the marked changes of TRIM22 during activation of crude T lymphocytes, in isolated subpopulations, TRIM22 expression was not significantly affected in spite of IL-2-induced or CD3/CD2/CD28-induced activation. In addition, in contrast to the TRIM22 mouse ortholog Rpt-1, TRIM22 did not affect levels of CD25 (IL-2R alpha) mRNA. Our data suggest a more complex role for TRIM22 during T lymphocyte activation than merely as an antiproliferative factor. TRIM22 probably has an activation stage-specific role connected to the paracrine crosstalk during T lymphocyte activation.
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| 4. |
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| 5. |
- Obad, Susanna
(författare)
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TRIM22/Staf50 - a novel target gene of the tumor suppressor p53
- 2007
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The tumor suppressor gene p53 is a transcription factor that mediates cell cycle arrest, apoptosis and differentiation. p53 mediated differentiation of leukemic cells depends on the transcriptional activity of p53 but so far no obvious differentiation inducing target gene has been identified. Using a cDNA microarray analysis, I identified TRIM22/Staf50 as a novel direct target gene to p53. The function of TRIM22 is largely unknown apart from being an interferon inducible protein and its involvement in inhibiting virus infection. TRIM22 belongs to the family of TRIM proteins (RBCC proteins) consisting of a RING finger, a B-box, a coiled-coil and a variable C-terminal. The TRIM proteins have been shown to be involved in cellular processes like virus infection, ubiquitination, differentiation and apoptosis. I have found that overexpression of TRIM22 increases cell death and co-localizes with the tumor suppressor PML. Interestingly, PML is also interferon inducible, a member of the TRIM family (TRIM19) and involved in functions like apoptosis and viral defense. Furthermore I found that TRIM22 have a role in hematopoietic differentiation and in T lymphocyte activation. Given that TRIM22 mediates cell death and has a role in differentiation and viral defense, I suggest that TRIM22 could be the link between p53 tumor suppression pathways and interferon response pathways. However, further experiments are necessary to reveal the mechanisms of TRIM22 in order to connect these two pathways.
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