geoscience.net logo
+ Resolve Article
+ Follow Us
Follow on FacebookFollow on Facebook
Follow on TwitterFollow on Twitter

+ Translate
+ Subscribe to Site Feed
GeoScience Most Shared ContentMost Shared Content

Spatiotemporally Regulated Ablation of Klf4 in Adult Mouse Corneal Epithelial Cells Results in Altered Epithelial Cell Identity and Disrupted Homeostasis


, : Spatiotemporally Regulated Ablation of Klf4 in Adult Mouse Corneal Epithelial Cells Results in Altered Epithelial Cell Identity and Disrupted Homeostasis. Investigative Ophthalmology & Visual Science 56(6): 3549-3558

In previous studies, conditional disruption of Klf4 in the developing mouse ocular surface from embryonic day 10 resulted in corneal epithelial fragility, stromal edema, and loss of conjunctival goblet cells, revealing the importance of Klf4 in ocular surface maturation. Here, we use spatiotemporally regulated ablation of Klf4 to investigate its functions in maintenance of adult corneal epithelial homeostasis. Expression of Cre was induced in ternary transgenic (Klf4(LoxP/LoxP)/Krt12(rtTA/rtTA)/Tet-O-Cre) mouse corneal epithelium by doxycycline administered through intraperitoneal injections and drinking water, to generate corneal epithelium-specific deletion of Klf4 (Klf4(Δ/ΔCE)). Corneal epithelial barrier function was tested by fluorescein staining. Expression of selected Klf4-target genes was determined by quantitative PCR (QPCR), immunoblotting, and immunofluorescent staining. Klf4 was efficiently ablated within 5 days of doxycycline administration in adult Klf4(Δ/ΔCE) corneal epithelium. The Klf4(Δ/ΔCE) corneal epithelial barrier function was disrupted, and the basal cells were swollen and rounded after 15 days of doxycycline treatment. Increased numbers of cell layers and Ki67-positive proliferating cells suggested deregulated Klf4(Δ/ΔCE) corneal epithelial homeostasis. Expression of tight junction proteins ZO-1 and occludin, desmosomal Dsg and Dsp, basement membrane laminin-332, and corneal epithelial-specific keratin-12 was decreased, while that of matrix metalloproteinase Mmp9 and noncorneal keratin-17 increased, suggesting altered Klf4(Δ/ΔCE) corneal epithelial cell identity. Ablation of Klf4 in the adult mouse corneas resulted in the absence of characteristic corneal epithelial cell differentiation, disrupted barrier function, and squamous metaplasia, revealing that Klf4 is essential for maintenance of the adult corneal epithelial cell identity and homeostasis.

US$19.90

PMID: 26047041

DOI: 10.1167/iovs.15-16463


Other references

Forth, Wolfgang, 1995: Potential toxic compounds in our environment: Challenge or cost of prosperity?. The goal of this contribution was the description of the possibilities as well as the limitations to which a toxicologist is confronted when evaluating potential toxic compounds to which human beings can be exposed during their lifetime. The numbe...

Moroder, L.; Jaeger, E.; Drees, F.; Geminer, M.; Knof, S.; Stelzel, H.P.; Thamm, P.; Bataille, D.; Domschke, S.; Et-Al, 1980: Structure function studies on gastro intestinal hormones 1. synthesis of secretin analogs and their biological and immunological properties. Syntheses by conventional procedures of the 3 analogs corresponding to the porcine secretin [SN] sequence crossed at position 6 by the N-terminal hexapeptide sequences of VIP [vasoactive intestinal polypeptide], GMP [gastric inhibitory polypeptide...

Lichtenberg, J.D.; Galler, F.B., 1987: The fundamental rule: a study of current usage. Members of the editorial boards of the Journal of the American Psychoanalytic Association, Psychoanalytic Quarterly, and Psychoanalytic Inquiry, plus selected analysts from Canada, France, and England, were asked how they presented the fundamental...

Glibert M., 1974: Some cenozoic turbinoliidae of the collections of the royal institute of natural sciences of belgium part 1 the genus turbinolia. Bulletin de l'Institut Royal des Sciences Naturelles de Belgique Sciences de la Terre 50(1): 1-27

Lytvynenko N.M.; Dzevaltovs'kyi A.K., 1972: Embryology of di ploid and tetra ploid forms of emilia flammea. Ukrayins'kyi Botanichnyi Zhurnal 29(5): 614-618

Cooper, R.F.; Dennis, S.M.; Harris, J.O., 1973: Fractionation of Listeria monocytogenes serotype 5. Bulk growth of L. monocytogenes serotype 5 gave a cell yield of 0.12 g/l. The cells were lyophilized, rehydrated, and disrupted by 40 minutes' sonication. Sixteen fractions were obtained by ammonium sulphate precipitation, chloroform extracti...

Granatelli D.; Blanc J J.; Penther P., 1977: Computerized phono cardiographic surveillance of patients fitted with valve prostheses part 2 symptoms of mal function of ball or disc prostheses. Annales de Cardiologie et d'Angeiologie 26(5): 365-371

Oberholzer, K.; Romaneehsen, B.; Kunz, P.; Kramm, T.; Thelen, M.; Kreitner, K-F., 2004: Contrast-enhanced 3D MR angiography of the pulmonary arteries with integrated parallel acquisition technique (iPAT) in patients with chronic-thromboembolic pulmonary hypertension CTEPH - sagittal or coronal acquisition?. Comparison of two different types of contrast-enhanced 3D-MR angiography (CE-MRA) with integrated parallel acquisition technique (iPAT) in patients with chronic-thromboembolic pulmonary hypertension (CTEPH) and evaluation whether sagittal acquisit...

Saade, J.S.; Abiad, B.; Jan, J.; Saadeh, D.; McCulley, J.P.; Bartley, J., 2017: Ocular Rosacea Causing Corneal Melt in an African American Patient and a Hispanic Patient. To discuss two rare presentations of ocular rosacea in a Hispanic patient and an African American patient with unusual ocular manifestations. Case  1: a 43-year-old Hispanic woman presented with right eye corneal perforation. Her prior medical...

Camargo M.E.; Rebonato C., 1969: Cross reactivity in fluorescence tests for trypanosoma and leishmania antibodies a simple inhibition procedure to ensure specific results human leishmania braziliensis trypanosoma cruzi. American Journal of Tropical Medicine & Hygiene 18(4): 500-505