Schlafen 3, a novel gene, regulates colonic mucosal growth during aging
Schlafen 3, a novel gene, regulates colonic mucosal growth during aging
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DOI：
10.1152/ajpgi.90726.2008
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发表时间：
2009-04-01
影响因子：
4.5
通讯作者：
Majumdar, Adhip P. N.
中科院分区：
文献类型：
--
作者：
Patel, Bhaumik B.;Yu, Yingjie;Majumdar, Adhip P. N.
尽管衰老与Fischer 344大鼠结肠黏膜增殖增加和细胞凋亡减少有关，但其调控机制尚不清楚。在幼年（4-6月龄）和老年（22-24月龄）Fischer 344大鼠新鲜分离的结肠粘膜细胞中进行基因表达谱分析（Illumina平台）。66个基因在幼龄动物和老龄动物结肠黏膜中差异表达（P < 0.05）。特别是增殖负调节因子schlafen 3在老龄大鼠结肠黏膜中的表达减少了8- 10倍。wortmannin在老龄大鼠结肠黏膜中抑制结肠粘膜增殖，刺激schlafen 3的表达，表明该基因具有生长调节作用。为了进一步确定schlafen 3基因的生长调控特性，我们在结肠癌HCT-116细胞中转染了schlafen 3 cDNA。这导致30-40%的细胞生长受到抑制，并伴有PCNA和cyclin D1的表达下降和视网膜母细胞瘤蛋白磷酸化降低。总之，我们目前的研究表明，一些参与增殖和凋亡的基因在年轻和老年大鼠结肠粘膜中表达不同。Schlafen 3是一种新的生长负调节因子，在老年人结肠黏膜中明显下调，可能在衰老过程中调节结肠黏膜生长。
Although aging is associated with increased proliferation and decreased apoptosis in the colonic mucosa of Fischer 344 rats, the regulatory mechanisms are poorly understood. Gene expression profiling (Illumina platform) was carried out in freshly isolated colonic mucosal cells from young (4-6 mo old) and aged (22-24 mo old) Fischer 344 rats. Sixty-six genes were differentially expressed in the colonic mucosa between young and old animals (P < 0.05). In particular, the expression of schlafen 3, a negative regulator of proliferation, was decreased by 8- to 10-fold in the colonic mucosa of aged rats. Administration of wortmannin, which inhibited colonic mucosal proliferation in the colonic mucosa of aged rats, stimulated the expression of schlafen 3, indicating a growth regulatory role of this gene. To further determine the growth regulatory properties of schlafen 3 gene, schlafen 3 cDNA was transfected in colon cancer HCT-116 cells. This resulted in a 30-40% inhibition of cellular growth, accompanied by decreased expression of PCNA and cyclin D1 and reduced phosphorylation of retinoblastoma protein. In conclusion, our present study demonstrates that several genes involved in proliferation and apoptosis are differentially expressed in the colonic mucosa of young and aged rats. Schlafen 3, a novel negative regulator of growth, which is markedly downregulated in the colonic mucosa of the aged, may play a role in regulating colonic mucosal growth during aging.