Significance of the S100A4 protein in psoriasis
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Significance of the S100A4 protein in psoriasis. / Zibert, John R; Skov, Lone; Thyssen, Jacob P; Jacobsen, Grete K; Grigorian, Mariam.
In: Journal of Investigative Dermatology, Vol. 130, No. 1, 01.01.2010, p. 150-60.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Significance of the S100A4 protein in psoriasis
AU - Zibert, John R
AU - Skov, Lone
AU - Thyssen, Jacob P
AU - Jacobsen, Grete K
AU - Grigorian, Mariam
PY - 2010/1/1
Y1 - 2010/1/1
N2 - The S100A4 protein is reported as a pivotal player in the tumor microenvironment with a metastasis-promoting function. Moreover, the upregulation of S100A4 is found in other non-malignant human disorders as cardiac and pulmonary systems and rheumatoid arthritis. In this study, we investigated the expression and significance of S100A4 in psoriasis. We found significant upregulation of S100A4 in the dermis of psoriatic skin compared with normal skin. This pattern of S100A4 expression differs considerably from that of other S100 proteins, S100A7 and S100A8/9, with predominant expression in the epidermis of psoriasis. Furthermore, we revealed a massive release of the biologically active forms of S100A4 from psoriatic skin. Interestingly, we found stabilization (increase) of p53 in the basal layer of epidermis in close proximity to cells expressing S100A4. To examine the possible implication of S100A4 in the pathogenesis of psoriasis, we analyzed the effect of S100A4 blocking antibodies in a human psoriasis xenograft SCID mouse model and observed a significant reduction of the epidermal thickness and impairment in cell proliferation and dermal vascularization. In conclusion, we showed strong upregulation and release of S100A4 in the upper dermis of psoriatic skin and found evidence indicating that S100A4 might actively contribute to the pathogenesis of psoriasis.
AB - The S100A4 protein is reported as a pivotal player in the tumor microenvironment with a metastasis-promoting function. Moreover, the upregulation of S100A4 is found in other non-malignant human disorders as cardiac and pulmonary systems and rheumatoid arthritis. In this study, we investigated the expression and significance of S100A4 in psoriasis. We found significant upregulation of S100A4 in the dermis of psoriatic skin compared with normal skin. This pattern of S100A4 expression differs considerably from that of other S100 proteins, S100A7 and S100A8/9, with predominant expression in the epidermis of psoriasis. Furthermore, we revealed a massive release of the biologically active forms of S100A4 from psoriatic skin. Interestingly, we found stabilization (increase) of p53 in the basal layer of epidermis in close proximity to cells expressing S100A4. To examine the possible implication of S100A4 in the pathogenesis of psoriasis, we analyzed the effect of S100A4 blocking antibodies in a human psoriasis xenograft SCID mouse model and observed a significant reduction of the epidermal thickness and impairment in cell proliferation and dermal vascularization. In conclusion, we showed strong upregulation and release of S100A4 in the upper dermis of psoriatic skin and found evidence indicating that S100A4 might actively contribute to the pathogenesis of psoriasis.
U2 - http://dx.doi.org/10.1038/jid.2009.206
DO - http://dx.doi.org/10.1038/jid.2009.206
M3 - Journal article
VL - 130
SP - 150
EP - 160
JO - Journal of Investigative Dermatology
JF - Journal of Investigative Dermatology
SN - 0022-202X
IS - 1
ER -
ID: 34124666