Novel proteins of the Stat (signal transducers and activators of transcription) family have been associated with proliferation and differentiation of certain cells; the role of these transcription factors in gut differentiation has not been examined. The purpose of this study was to determine whether the cellular levels and actual binding of the Stat proteins are altered with intestinal differentiation using the Caco-2 cell line that spontaneously differentiates to a small bowel phenotype after confluency. We found that both Stat3 and Stat5 protein levels were increased in preconfluent and confluent Caco-2 cells; levels then decreased with postconfluency. Mobility shift assays demonstrated maximal binding of Stat3 and Stat5 at confluency and, similar to protein levels, binding activity decreased with postconfluency. The intestinal differentiation marker gene sucrase-isomaltase was increased by postconfluent day 1 with maximal levels by day 6. The progressive decrease of Stat3 and Stat5 protein levels and binding activity, occurring at a time associated with increased Caco-2 cell differentiation, suggests that a decrease in the cellular levels of these proteins may potentially play a role in subsequent intestinal cell differentiation. Delineating the cellular mechanisms responsible for intestinal differentiation is crucial to a better understanding of both normal gut development and aberrant gut growth.
|Number of pages||8|
|Journal||Journal of Gastrointestinal Surgery|
|State||Published - 1999|
Bibliographical noteFunding Information:
Stimulation of downstream transcription factors by various growth factors and cytokines is responsible for their ultimate effects on cellular growth and differentiation. An important advance in the understanding of the mechanisms by which these agents regulate cellular functions has been the identification and characterization of the Stat (signal transducers and activators of transcription) signal transduction pathway. 5-9 To date, six distinct but homologous members of the Stat family have been identified (designated Statl to Star6)) ° Stat proteins 1, 3, and 5 are more ubiquitous, better characterized, and have been demonstrated to play a role in cellular proliferation, differentiation, and apoptosis.11-18 Ill contrast, the remaining Stat proteins are relatively tissue specific and appear to participate more in immune function. ~° The Stat pro- From Department of Surgery,T he Universityo f Texas Medical Branch, Galveston, Tex. (Dr. Wang is a visiting scientist from the Department of Surgery, People's Hospital, BeijingM edical University,B eijing, China.) Supported by grants R01 DK48498, R01 AG10885, and P01 DK35608 from the National Institutes of Health and the James E. Thompson Memorial Foundation. Presented at the Thirty-Ninth AnnualM eeting of The Societyf or Surgeryo f the AlimentaryT ract, New Orleans, La., May 17-20, 1998. Reprint requests: B. Mark Evers, M.D., Department of Surgery,T he Universityo f TexasM edical Branch, 301 UniversityB lvd., Galveston, TX 77555-0533.
- Intestinal differentiation
- Signal transduction pathways
- Stat proteins
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