Overexpression of bone morphogenetic protein-6 (BMP-6) in the epidermis of transgenic mice: inhibition or stimulation of proliferation depending on the pattern of transgene expression and formation of psoriatic lesions.
Overexpression of bone morphogenetic protein-6 (BMP-6) in the epidermis of transgenic mice: inhibition or stimulation of proliferation depending on the pattern of transgene expression and formation of psoriatic lesions.
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DOI：
10.1083/jcb.135.1.227
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发表时间：
1996-10
影响因子：
7.8
通讯作者：
Kaiser, S
中科院分区：
文献类型：
--
作者：
Blessing, M;Schirmacher, P;Kaiser, S
骨形态发生蛋白-6（BMP-6）属于TGF-β相关生长因子家族。在发育中的表皮中，BMP- 6的表达与分层的开始一致。表达持续围产期，但产后6天后下降，虽然它仍然可以在成人皮肤中检测到逆转录-聚合酶链反应（RT-PCR）分析。我们组成性地过度表达BMP-6在基底层的毛囊间表皮的转基因小鼠使用角蛋白10启动子。所有表达转基因的小鼠的皮肤都出现异常，表明存在活性转基因衍生因子。根据转基因表达的模式，对增殖和分化的影响完全相反。BMP-6转基因的强而均匀的表达导致胚胎和围产期表皮细胞增殖的严重抑制，但对分化有边际效应。转基因的弱和斑片状表达引起成人表皮的强烈过度增殖和角化不全，以及通常的分化模式的严重扰动。这些扰动包括角蛋白和整合素表达的变化。与真皮和表皮中的炎性浸润一起，这些方面呈现人类皮肤病的所有典型组织学和生物化学特征：银屑病。
Bone morphogenetic protein-6 (BMP-6) belongs to the family of TGF-beta- related growth factors. In the developing epidermis, expression of BMP- 6 coincides with the onset of stratification. Expression persists perinatally but declines after day 6 postpartum, although it can still be detected in adult skin by reverse transcriptase-polymerase chain reaction (RT-PCR) analysis. We constitutively overexpressed BMP-6 in suprabasal layers of interfollicular epidermis in transgenic mice using a keratin 10 promoter. All mice expressing the transgene developed abnormalities in the skin, indicating an active transgene-derived factor. Depending on the pattern of transgene expression, the effects on proliferation and differentiation were completely opposite. Strong and uniform expression of the BMP-6 transgene resulted in severe repression of cell proliferation in embryonic and perinatal epidermis but had marginal effects on differentiation. Weaker and patchy expression of the transgene evoked strong hyperproliferation and parakeratosis in adult epidermis and severe perturbations of the usual pattern of differentiation. These perturbations included changes in the expression of keratins and integrins. Together with an inflammatory infiltrate both in the dermis and in the epidermis, these aspects present all typical histological and biochemical hallmarks of a human skin disease: psoriasis.
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影响因子：
7.8
作者：
Gitelman, S E;Kobrin, M S;Ye, J Q;Lopez, A R;Lee, A;Derynck, R
通讯作者：
Derynck, R
DOI：
10.1073/pnas.91.12.5528
发表时间：
1994-06-07
影响因子：
11.1
作者：
DROZDOFF, V;WALL, NA;PLEDGER, WJ
通讯作者：
PLEDGER, WJ
DOI：
10.1073/pnas.93.5.2116
发表时间：
1996-03-05
影响因子：
11.1
作者：
Bullard, DC;ScharffetterKochanek, K;Beaudet, AL
通讯作者：
Beaudet, AL
DOI：
10.1073/pnas.86.12.4554
发表时间：
1989-06-01
影响因子：
11.1
作者：
LYONS, K;GRAYCAR, JL;DERYNCK, R
通讯作者：
DERYNCK, R
DOI：
10.1002/tcm.1770150103
发表时间：
1995-01-01
期刊：
TERATOGENESIS CARCINOGENESIS AND MUTAGENESIS
影响因子：
--
作者：
BLESSING, M;NANNEY, LB;HOGAN, BLM
通讯作者：
HOGAN, BLM