Novel function of keratins 5 and 14 in proliferation and differentiation of stratified epithelial cells.
Novel function of keratins 5 and 14 in proliferation and differentiation of stratified epithelial cells.
复制标题
角蛋白5和14在分层上皮细胞的增殖和分化中的新功能。
DOI：
10.1091/mbc.e10-08-0703
复制
发表时间：
2011-11
影响因子：
3.3
通讯作者：
Vaidya MM
中科院分区：
文献类型：
--
作者：
Alam H;Sehgal L;Kundu ST;Dalal SN;Vaidya MM
角蛋白在复层上皮中的表达在鳞状细胞分化过程中受到严格调节。角蛋白5和14在有丝分裂活跃的基底层细胞中表达，但它们的功能还不清楚。本文报道了K14在复层上皮细胞中调节细胞增殖/分化的可能作用。角蛋白是细胞质中的中间丝蛋白，在上皮组织中以位点特异性和分化依赖性的方式优先表达。复层上皮中角蛋白丝的复杂网络在鳞状细胞分化过程中受到严格调控。角蛋白14（K14）在有丝分裂活性的基底层细胞中表达，沿着其伴侣角蛋白5（K5），并且它们的表达随着细胞分化而下调。除了K14的细胞保护功能外，对K14的调节功能知之甚少，因为K14敲除小鼠显示出出生后的致死性。在这项研究中，K14的表达抑制RNA干扰细胞系来源于复层上皮细胞研究K14在上皮稳态的功能。K14敲除克隆显示K14伴侣K5的水平显著降低。这些细胞显示细胞增殖减少和细胞周期进展延迟，沿着磷酸化Akt水平降低。K14敲除细胞也表现出激活的Notch 1，外皮蛋白和K1的水平增加。此外，K14敲减的AW 13516细胞显示出致瘤性显著降低。我们的研究结果表明，K5和K14可能在维持复层上皮基底层的细胞增殖潜力，调节磷脂酰肌醇3-激酶/Akt介导的细胞增殖和/或Notch 1依赖的细胞分化中发挥作用。
Keratin expression in stratified epithelia is tightly regulated during squamous cell differentiation. Keratins 5 and 14 are expressed in mitotically active basal layer cells, but their function is not well defined. Reported here is the possible role of K14 in regulation of cell proliferation/differentiation in stratified epithelial cells. Keratins are cytoplasmic intermediate filament proteins preferentially expressed by epithelial tissues in a site-specific and differentiation-dependent manner. The complex network of keratin filaments in stratified epithelia is tightly regulated during squamous cell differentiation. Keratin 14 (K14) is expressed in mitotically active basal layer cells, along with its partner keratin 5 (K5), and their expression is down-regulated as cells differentiate. Apart from the cytoprotective functions of K14, very little is known about K14 regulatory functions, since the K14 knockout mice show postnatal lethality. In this study, K14 expression was inhibited using RNA interference in cell lines derived from stratified epithelia to study the K14 functions in epithelial homeostasis. The K14 knockdown clones demonstrated substantial decreases in the levels of the K14 partner K5. These cells showed reduction in cell proliferation and delay in cell cycle progression, along with decreased phosphorylated Akt levels. K14 knockdown cells also exhibited enhanced levels of activated Notch1, involucrin, and K1. In addition, K14 knockdown AW13516 cells showed significant reduction in tumorigenicity. Our results suggest that K5 and K14 may have a role in maintenance of cell proliferation potential in the basal layer of stratified epithelia, modulating phosphatidylinositol 3-kinase/Akt–mediated cell proliferation and/or Notch1-dependent cell differentiation.