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Am J Physiol Gastrointest Liver Physiol 296: G955-G962, 2009. First published February 19, 2009; doi:10.1152/ajpgi.90726.2008
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MUCOSAL BIOLOGY

Schlafen 3, a novel gene, regulates colonic mucosal growth during aging

Bhaumik B. Patel,1,2,4 Yingjie Yu,1,2 Jianhua Du,1,2 Arun K. Rishi,1,4 Fazlul H. Sarkar,3,4 Adi L. Tarca,4 Anil Wali,1,4 and Adhip P. N. Majumdar1,2,4

1Veterans Administration Medical Center, Departments of 2Medicine and 3Pathology, and 4Karmanos Cancer Institute, Wayne State University, Detroit, Michigan

Submitted 26 December 2008 ; accepted in final form 16 February 2009

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.

aging; gastrointestinal mucosa; cancer; proliferation; microarrays


Address for reprint requests and other correspondence: A. P. N. Majumdar, 4646 John R St., Detroit, MI 48201 (e-mail: a.majumdar{at}wayne.edu)






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