| 1. |
- Sonkoly, Enikö, et al.
(author)
-
MicroRNAs : novel regulators involved in the pathogenesis of psoriasis?
- 2007
-
In: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 2:7
-
Journal article (peer-reviewed)abstract
- MicroRNAs are a recently discovered class of posttranscriptional regulators of gene expression with critical functions in health and disease. Psoriasis is the most prevalent chronic inflammatory skin disease in adults, with a substantial negative impact on the patients' quality of life. Here we show for the first time that psoriasis-affected skin has a specific microRNA expression profile when compared with healthy human skin or with another chronic inflammatory skin disease, atopic eczema. Among the psoriasis-specific microRNAs, we identified leukocyte-derived microRNAs and one keratinocyte-derived microRNA, miR-203. In a panel of 21 different human organs and tissues, miR-203 showed a highly skin-specific expression profile. Among the cellular constituents of the skin, it was exclusively expressed by keratinocytes. The up-regulation of miR-203 in psoriatic plaques was concurrent with the down-regulation of an evolutionary conserved target of miR-203, suppressor of cytokine signaling 3 (SOCS-3), which is involved in inflammatory responses and keratinocyte functions. Our results suggest that microRNA deregulation is involved in the pathogenesis of psoriasis and contributes to the dysfunction of the cross talk between resident and infiltrating cells. Taken together, a new layer of regulatory mechanisms is involved in the pathogenesis of chronic inflammatory skin diseases.
|
|
| 2. |
|
|
| 3. |
- Sääf, Annika, et al.
(author)
-
Characterization of EGFR and ErbB2 expression in atopic dermatitis patients.
- 2012
-
In: Archives of Dermatological Research. - : Springer Science and Business Media LLC. - 0340-3696 .- 1432-069X. ; 304:10, s. 773-80
-
Journal article (peer-reviewed)abstract
- Atopic dermatitis (AD) is one of the most common chronic inflammatory skin diseases in industrialized countries. To identify candidate genes involved in the pathogenesis of AD, we previously undertook a genome-wide approach using DNA microarrays. A transcript encoding the epidermal growth factor receptor (EGFR) was found to be among the down-regulated transcripts in AD skin. Here, we further investigated the expression pattern of two EGFR family members (EGFR and ErbB2) in AD skin on a protein level. Immunohistochemical (IHC) analysis of EGFR and ErbB2 showed decreased expression of EGFR and ErbB2 proteins in AD lesional skin as compared to skin from healthy individuals. Interestingly, we found that EGFR and ErbB2 were reciprocally expressed in an in vitro model of keratinocyte proliferation and differentiation, paralleling the expression patterns found in epidermis of healthy skin. The highest levels of EGFR transcripts were found in proliferating cells, while ErbB2 was found in differentiated cells. We show that blocking EGFR activity combined with co-stimulation of the Th2-cytokine IL4 in keratinocytes leads to induction of the inflammatory chemokine CCL26/eotaxin-3 in vitro. Accordingly, increased CCL26 transcriptional levels were observed in AD lesional skin. Taken together, suppression of EGFR may contribute to the pathogenesis of AD via the regulation of inflammatory chemokines.
|
|
| 4. |
|
|
| 5. |
- Sääf, Annika, 1970-
(author)
-
Insertion and Topology of Inner Membrane Proteins in Escherichia coli
- 1999
-
Doctoral thesis (other academic/artistic)abstract
- Integral membrane proteins are found in all cellular membranes and fulfil many of the functions that are central to life. They maintain the membrane structure, but are also involved in the regulation of different cellular processes. All membrane proteins destined for the plasma membrane or that are to be secreted are synthesised in the cytoplasm, and to perform their function they have to be transported to the membrane and correctly inserted into the membrane.Protein trafficking within the cell is complex and has to be precisely controlled. In the Gram-negative bacterial cell, there are five different compartments: the cytoplasm, the inner- and outer membranes, the periplasm and the cell-exterior, and in the eukaryotic cell with its different organelles, there are even more compartments for a protein to end up in. Newly synthesised polypeptide chains are made with an address-tag, the signal peptide, that is recognised by factors in the cytoplasm and thus allowing targeting of the polypeptide chain to the correct membrane.In this thesis, research has been focused on integral membrane proteins destined for the bacterial inner membrane. Questions concerning targeting of membrane proteins, their insertion into the membrane, and finally their orientation within the membrane are addressed. I have analysed the degree of sec-dependence and the assembly properties for the E.coli inner membrane protein MalF. Topological studies have been performed on YidC, a novel E.coli protein homologues to the mitochondrial Oxa1p. An additional topological study has been performed, but from an evolutionary perspective, on two E.coli proteins, ORF193 and YdgQ. Although, they belong to the same family and are strongly related, they have opposite topologies which could suggest that evolution can impart different membrane topologies on strongly related proteins by reshuffling of positively charged residues. Detailed studies of the characterisation of transmembrane segments and turn formation in membrane proteins are also reported.
|
|
| 6. |
- van der Valk, Ralf J P, et al.
(author)
-
A novel common variant in DCST2 is associated with length in early life and height in adulthood.
- 2015
-
In: Human molecular genetics. - : Oxford University Press (OUP). - 1460-2083 .- 0964-6906. ; 24:4, s. 1155-68
-
Journal article (peer-reviewed)abstract
- Common genetic variants have been identified for adult height, but not much is known about the genetics of skeletal growth in early life. To identify common genetic variants that influence fetal skeletal growth, we meta-analyzed 22 genome-wide association studies (Stage 1; N = 28 459). We identified seven independent top single nucleotide polymorphisms (SNPs) (P < 1 × 10(-6)) for birth length, of which three were novel and four were in or near loci known to be associated with adult height (LCORL, PTCH1, GPR126 and HMGA2). The three novel SNPs were followed-up in nine replication studies (Stage 2; N = 11 995), with rs905938 in DC-STAMP domain containing 2 (DCST2) genome-wide significantly associated with birth length in a joint analysis (Stages 1 + 2; β = 0.046, SE = 0.008, P = 2.46 × 10(-8), explained variance = 0.05%). Rs905938 was also associated with infant length (N = 28 228; P = 5.54 × 10(-4)) and adult height (N = 127 513; P = 1.45 × 10(-5)). DCST2 is a DC-STAMP-like protein family member and DC-STAMP is an osteoclast cell-fusion regulator. Polygenic scores based on 180 SNPs previously associated with human adult stature explained 0.13% of variance in birth length. The same SNPs explained 2.95% of the variance of infant length. Of the 180 known adult height loci, 11 were genome-wide significantly associated with infant length (SF3B4, LCORL, SPAG17, C6orf173, PTCH1, GDF5, ZNFX1, HHIP, ACAN, HLA locus and HMGA2). This study highlights that common variation in DCST2 influences variation in early growth and adult height.
|
|
