Transcription factor NF-κB participates in regulation of epithelial cell turnover in the colon

• Published in: American journal of physiology: Gastrointestinal and liver physiology 2000-12, Vol.279 (6), p.G1282-G1291
• Main Authors: Inan, Mehmet Sait, Tolmacheva, Veronica, Wang, Qiang-Shu, Rosenberg, Daniel W., Giardina, Charles
• Format: Article
• Language: English
• ISSN: 0193-1857; 1522-1547
• DOI: 10.1152/ajpgi.2000.279.6.G1282

The transcription factor nuclear factor (NF)-κB regulates the expression of genes that can influence cell proliferation and death. Here we analyze the contribution of NF-κB to the regulation of epithelial cell turnover in the colon. Immunohistochemical, immunoblot, and DNA binding analyses indicate that NF-κB complexes change as colonocytes mature: p65-p50 complexes predominate in proliferating epithelial cells of the colon, whereas the p50-p50 dimer is prevalent in mature epithelial cells. NF-κB1 (p50) knockout mice were used to study the role of NF-κB in regulating epithelial cell turnover. Knockout animals lacked detectable NF-κB DNA binding activity in isolated epithelial cells and had significantly longer crypts with a more extensive proliferative zone than their wild-type counterparts (as determined by proliferating cell nuclear antigen staining and in vivo bromodeoxyuridine labeling). Gene expression profiling reveals that the NF-κB1 knockout mice express the potentially growth-enhancing tumor necrosis factor (TNF)-α and nerve growth factor-α genes at elevated levels, with in situ hybridization localizing some of the TNF-α expression to epithelial cells. TNF-α is NF-κB regulated, and its upregulation in NF-κB1 knockouts may result from an alleviation of p50-p50 repression. NF-κB complexes may therefore influence cell proliferation in the colon through their ability to selectively activate and/or repress gene expression.