Basonuclin-null mutation impairs homeostasis and wound repair in mouse corneal epithelium.
Basonuclin-null mutation impairs homeostasis and wound repair in mouse corneal epithelium.
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DOI：
10.1371/journal.pone.0001087
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发表时间：
2007-10-31
期刊：
影响因子：
3.7
通讯作者：
Tseng, Hung
中科院分区：
文献类型：
--
作者：
Zhang, Xiaohong;Tseng, Hung
角膜上皮稳态和伤口修复至少需要两个细胞过程：细胞增殖和细胞间粘附。这些过程微妙地平衡，以确保维持正常的上皮功能。在伤口愈合过程中，这些过程必须协调重新编程，以实现快速上皮化。 Basonuclin (Bnc1) 是一种细胞类型特异性转录因子，主要在复层上皮（例如角膜上皮、表皮和食管上皮）的增殖角质形成细胞以及睾丸和卵巢中的配子发生细胞中表达。我们之前的工作表明，basonuclin 可以调节核糖体 RNA 基因 (rDNA) 和涉及染色质结构、转录调控、细胞间连接/通讯、离子通道和细胞内运输的基因的转录。然而，基底核蛋白在角质形成细胞中的作用尚未在体内得到证实。在这里，我们发现基底核蛋白缺失突变会破坏角膜上皮稳态，并通过损害细胞增殖来延迟伤口愈合。在基底核蛋白缺失的角膜上皮中，RNA 聚合酶 I (Pol I) 转录受到干扰。这种扰动是独特的，因为它影响 rDNA 子集的转录本。 Basonuclin 缺失突变还会扰乱编码染色质结构蛋白组蛋白 3 和 HMG2、转录因子 Gli2、间隙连接蛋白连接蛋白 43 和粘附 E-钙粘蛋白的基因的 RNA 聚合酶 II (Pol II) 转录本。在大多数情况下，观察到 mRNA 和蛋白质水平的协同变化。然而，对于E-钙粘蛋白，尽管其mRNA水平显着增加，但其蛋白质水平却降低了。总之，我们的研究确立了 basonuclin 作为角膜上皮稳态和维持的调节剂。 Basonuclin 可能协调核糖体 RNA 基因 (rDNA) 子集和一组蛋白质编码基因在细胞过程中的功能，这些基因对于细胞增殖的调节至关重要。
At least two cellular processes are required for corneal epithelium homeostasis and wound repair: cell proliferation and cell-cell adhesion. These processes are delicately balanced to ensure the maintenance of normal epithelial function. During wound healing, these processes must be reprogrammed in coordination to achieve a rapid re-epithelialization. Basonuclin (Bnc1) is a cell-type-specific transcription factor expressed mainly in the proliferative keratinocytes of stratified epithelium (e.g., corneal epithelium, epidermis and esophageal epithelium) and the gametogenic cells in testis and ovary. Our previous work suggested that basonuclin could regulate transcription of ribosomal RNA genes (rDNA) and genes involved in chromatin structure, transcription regulation, cell-cell junction/communication, ion-channels and intracelllular transportation. However, basonuclin's role in keratinocytes has not been demonstrated in vivo. Here we show that basonuclin-null mutation disrupts corneal epithelium homeostasis and delays wound healing by impairing cell proliferation. In basonuclin-null cornea epithelium, RNA polymerase I (Pol I) transcription is perturbed. This perturbation is unique because it affects transcripts from a subset of rDNA. Basonuclin-null mutation also perturbs RNA polymerase II (Pol II) transcripts from genes encoding chromatin structure proteins histone 3 and HMG2, transcription factor Gli2, gap-junction protein connexin 43 and adheren E-cadherin. In most cases, a concerted change in mRNA and protein level is observed. However, for E-cadherin, despite a notable increase in its mRNA level, its protein level was reduced. In conclusion, our study establishes basonuclin as a regulator of corneal epithelium homeostasis and maintenance. Basonuclin likely coordinates functions of a subset of ribosomal RNA genes (rDNA) and a group of protein coding genes in cellular processes critical for the regulation of cell proliferation.
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DOI：
10.1073/pnas.96.17.9628
发表时间：
1999-08-17
影响因子：
11.1
作者：
Iuchi, S;Green, H
通讯作者：
Green, H
影响因子：
4.6
作者：
Ma, J;Zeng, FY;Tseng, H
通讯作者：
Tseng, H
影响因子：
64.5
作者：
Picard, F;Géhin, M;Auwerx, J
通讯作者：
Auwerx, J
影响因子：
4.4
作者：
Romano, RA;Li, HX;Sinha, S
通讯作者：
Sinha, S
DOI：
10.1073/pnas.94.15.7948
发表时间：
1997-07-22
影响因子：
11.1
作者：
Iuchi, S;Green, H
通讯作者：
Green, H