EXPRESSION AND GROWTH-INHIBITORY EFFECT OF DECAPENTAPLEGIC VG-RELATED PROTEIN-6 - EVIDENCE FOR A REGULATORY ROLE IN KERATINOCYTE DIFFERENTIATION
EXPRESSION AND GROWTH-INHIBITORY EFFECT OF DECAPENTAPLEGIC VG-RELATED PROTEIN-6 - EVIDENCE FOR A REGULATORY ROLE IN KERATINOCYTE DIFFERENTIATION
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DOI：
10.1073/pnas.91.12.5528
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发表时间：
1994-06-07
影响因子：
11.1
通讯作者：
PLEDGER, WJ
中科院分区：
文献类型：
--
作者：
DROZDOFF, V;WALL, NA;PLEDGER, WJ
Decapentaplegic Vg相关蛋白6（DVR-6或骨形态发生蛋白BMP-6）是转化生长因子β超家族的DVR亚组的成员，转化生长因子β超家族是一大组多功能信号传导多肽，其表达为从较大前体蛋白水解切割的分泌的二硫键键二聚体。DVR-6在复层鳞状上皮细胞分化的有丝分裂后层中的主要表达强烈表明DVR-6在调节上皮分化中的作用。在原代小鼠角质形成细胞诱导分化悬浮培养在甲基纤维素中，DVR-6的mRNA和蛋白质的新的表达中检测到8小时内的大多数悬浮细胞，这之前的基底上角蛋白K1和K10的表达诱导。为了检验DVR-6是角质形成细胞生长调节因子的假设，使用表达人DVR-6的逆转录病毒表达载体感染未分化基底细胞的附着培养物。DVR-6在分化前的原代小鼠角质形成细胞中的表达导致在条件培养基中的prepro和加工（pro区域）形式的分泌和细胞生长的显著抑制。这些发现表明DVR-6对细胞生长的抑制可能是角质形成细胞分化的主要步骤。
Decapentaplegic Vg-related protein 6 (DVR-6 or bone morphogenetic protein BMP-6) is a member of the DVR subgroup of the transforming growth factor beta superfamily, a large group of multifunctional signaling polypeptides that are expressed as secreted disulfide-bonded dimers proteolytically cleaved from larger precursors. The predominant expression of DVR-6 in the differentiating postmitotic layers of stratified squamous epithelia strongly suggests a role for DVR-6 in regulation of epithelial differentiation. In primary mouse keratinocytes induced to differentiate by suspension culture in methylcellulose, new expression of DVR-6 mRNA and protein was detected within 8 h among a majority of the suspended cells, which preceded the induction of expression of the suprabasal keratins K1 and K10. To test the hypothesis that DVR-6 is a keratinocyte growth regulatory factor, a retroviral expression vector expressing human DVR-6 was used to infect attached cultures of undifferentiated basal cells. Expression of DVR-6 in primary mouse keratinocytes before differentiation resulted in the secretion of prepro and processed (pro region) forms in the conditioned medium and a dramatic inhibition of cell growth. These findings suggest that inhibition of cell growth by DVR-6 may be a primary step in keratinocyte differentiation.