Conditional Deletion of the Mouse <i>Klf4</i> Gene Results in Corneal Epithelial Fragility, Stromal Edema, and Loss of Conjunctival Goblet Cells

Swamynathan, Sudha; Katz, Jonathan P.; Kaestner, Klaus H.; Ashery‐Padan, Ruth; Crawford, M; Piatigorsky, Joram

doi:10.1128/mcb.00846-06

Cited by 117 publications

(172 citation statements)

References 65 publications

Supporting

Mentioning

154

Contrasting

Order By: Relevance

“…In contrast, overexpression of KLF4 in the skin accelerates the formation of the epidermal barrier (Jaubert et al, 2003). The role extends to other multilayered epithelia, as conditional deletion in the cornea leads to epithelial fragility (Swamynathan et al, 2007). KLF4 belongs to a large family of Kruppel-like activators with zinc-finger DNA-binding domains, recognizing the common GC boxes found in many, if not most, promoters (Kaczynski et al, 2003).…”

mentioning

confidence: 99%

Mutant p53 subverts p63 control over KLF4 expression in keratinocytes

et al. 2010

View full text Add to dashboard Cite

Genetic experiments established that p63 is crucial for the development and maintenance of pluri-stratified epithelia and KLF4 for the barrier function of the skin. KLF4 is one of the factors that reprogram differentiated cells to iPS. We investigated the relationship between p63 and KLF4 using RNA interference, overexpression, chromatin immunoprecipitation and transient transfections with reporter constructs. We find that p63 directly represses KLF4 in normal keratinocytes (KCs) by binding to upstream promoter sites. Unlike p63, KLF4 levels are high in the upper layers of human skin and increase upon differentiation of KCs in vitro. In HaCaT KCs, which harbor two mutant alleles of p53, inactivation of p63 and of mutant p53 leads to KLF4 repression. p63 and p53 mutants are bound to sites in the KLF4 core promoter. Importantly, expression of the H179Y and R282Q p53 mutants in primary KCs is sufficient to activate endogenous KLF4. Finally, immunohistochemical analysis of tissue arrays confirms increased coexpression of KLF4 and mutant p53 in squamous cell carcinomas. Our data indicate that suppression of KLF4 is part of the growth-promoting strategy of p63 in the lower layers of normal epidermis, and that tumor-predisposing p53 mutations hijack p63 to a different location on the promoter, turning it into an activator of this reprogramming factor.

show abstract

mentioning

confidence: 99%

Mutant p53 subverts p63 control over KLF4 expression in keratinocytes

et al. 2010

View full text Add to dashboard Cite

show abstract

“…Tissue-specific ablation of Klf4 in mouse stomach results in increased proliferation and altered differentiation of the gastric epithelia (3). In the eye, conditional knock-out of Klf4 results in abnormal corneal epithelium and lack of goblet cells in the conjunctiva (4). As such, Klf4 is implicated in a variety of cellular differentiation and proliferation processes by activating or repressing transcriptional activity of multiple genes.…”

mentioning

confidence: 99%

Smooth and Cardiac Muscle-selective Knock-out of Krüppel-like Factor 4 Causes Postnatal Death and Growth Retardation

Yoshida

Gan

Franke

et al. 2010

Journal of Biological Chemistry

View full text Add to dashboard Cite

Krüppel-like factor 4 (Klf4) is a transcription factor involved in differentiation and proliferation in multiple tissues. We demonstrated previously that tamoxifen-induced deletion of the Klf4 gene in mice accelerated neointimal formation but delayed down-regulation of smooth muscle cell differentiation markers in carotid arteries following injury. To further determine the role of Klf4 in the cardiovascular system, we herein derived mice deficient for the Klf4 gene in smooth and cardiac muscle using the SM22␣ promoter (SM22␣-CreKI ؉ /Klf4 loxP/loxP mice). SM22␣-CreKI؉ /Klf4 loxP/loxP mice were born at the expected Mendelian ratio, but they gradually died after birth. Although ϳ40% of SM22␣-CreKI ؉ /Klf4 loxP/loxP mice survived beyond postnatal day 28, they exhibited marked growth retardation. In wild-type mice, Klf4 was expressed in the heart from late embryonic development through adulthood, whereas it was not expressed in smooth muscle. No changes were observed in morphology or expression of smooth muscle cell differentiation markers in vessels of SM22␣-CreKI ؉ /Klf4 loxP/loxP mice. Of interest, cardiac output was significantly decreased in SM22␣-CreKI ؉ /Klf4 loxP/loxP mice, as determined by magnetic resonance imaging. Moreover, a lack of Klf4 in the heart resulted in the reduction in expression of multiple cardiac genes, including Gata4. In vivo chromatin immunoprecipitation assays on the heart revealed that Klf4 bound to the promoter region of the Gata4 gene. Results provide novel evidence that Klf4 plays a key role in late fetal and/or postnatal cardiac development.

show abstract

“…Ablation of KLF4 leads to increased proliferation and altered differentiation in the gastric epithelium of mice, and the absent expression of KLF4 in human gastric cancer suggests that failure to activate KLF4 during normal cellular differentiation is a common feature of gastric cancers (8). KLF4 also induces postnatal maturation of corneal epithelium and maintenance of the ocular surface via up-regulating the expression of KRT12 and aquaporin 5 (9). Analysis of microarray data shows that nine KRT genes are up-regulated by KLF4, seven of which are located in a specific region on chromosome 12 (10).…”

mentioning

confidence: 99%

Krüppel-like Factor 4 Promotes Esophageal Squamous Cell Carcinoma Differentiation by Up-regulating Keratin 13 Expression

Yuan

et al. 2015

Journal of Biological Chemistry

View full text Add to dashboard Cite

Background:The transcriptional regulation of keratin (KRT) 13 and its underlying mechanism has not been fully elucidated. Results: Up-regulation of KRT13 by Krüppel-like factor 4 (KLF4) is mediated through GKRE in the KRT13 promoter. Conclusion: KLF4 induces differentiation of ESCC by promoting KRT13 transcription. Significance: KLF4 plays a significant and previously unrecognized role in regulation of KRT13 and cell differentiation.

show abstract

Conditional Deletion of the Mouse Klf4 Gene Results in Corneal Epithelial Fragility, Stromal Edema, and Loss of Conjunctival Goblet Cells

Cited by 117 publications

References 65 publications

Mutant p53 subverts p63 control over KLF4 expression in keratinocytes

Mutant p53 subverts p63 control over KLF4 expression in keratinocytes

Smooth and Cardiac Muscle-selective Knock-out of Krüppel-like Factor 4 Causes Postnatal Death and Growth Retardation

Krüppel-like Factor 4 Promotes Esophageal Squamous Cell Carcinoma Differentiation by Up-regulating Keratin 13 Expression

Contact Info

Product

Resources

About