Schlafen-3: a novel regulator of intestinal differentiation.
Schlafen-3 (Slfn-3), a novel gene, has been shown to be a negative regulator of proliferation. The current investigation was undertaken to determine whether Slfn-3 might play a role in regulating cellular differentiation. Butyric acid, a short chain fatty acid, which induced differentiation of intestinal cells as evidenced by increased alkaline phosphatase (ALP) activity in the rat small intestinal IEC-6 cells, also produced a marked increase in Slfn-3 expression. Furthermore, overexpression of Slfn-3 caused stimulation of ALP activity in IEC-6 cells, which was exacerbated by butyrate. On the other hand, downregulation of Slfn-3 by slfn-3-si-RNA greatly attenuated the butyrate-mediated induction of differentiation of IEC-6 cells. Additionally, we observed that increased expression of Slfn-3 in colon cancer HCT-116 cells stimulated TGF-beta expression and modulated expression of its downstream effectors as evidenced by increased expression of p27kip1 and downregulation of CDK-2. In addition, Slfn-3 increases E-cadherin expression but downregulates beta-catenin. In conclusion, our data show that Slfn-3 plays a critical role in regulating intestinal mucosal differentiation. Furthermore our data also show that TGF-beta signaling pathway plays an important role in mediating slfn-3 induced differentiation.
Patel
Vaishali B
VB
Veterans Affairs Medical Center, Wayne State University, Detroit, MI 48201, USA.
Yu
Yingjie
Y
Das
Jayanta K
JK
Patel
Bhaumik B
BB
Majumdar
Adhip P N
AP
D000818:Animals; D002087:Butyrates / Q000494:pharmacology; D015820:Cadherins / Q000096:biosynthesis / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics; D045744:Cell Line, Tumor; D006801:Humans; D007413:Intestinal Mucosa / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D007422:Intestines / Q000166:cytology* / Q000187:drug effects; D011506:Proteins / Q000235:genetics / Q000502:physiology*; D034741:RNA, Small Interfering / Q000235:genetics; D051381:Rats; D016211:Transforming Growth Factor alpha / Q000096:biosynthesis
D002087:Butyrates; D015820:Cadherins; D011506:Proteins; D034741:RNA, Small Interfering; C541111:Slfn4 protein, rat; D016211:Transforming Growth Factor alpha
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