The Expression and Role of Krüppel-Like Factor 4 in Psoriasis
2
조회
0
다운로드
1
인용
0
참고문헌
키워드
초록
Background: Krüppel-like factor 4 (KLF4) is a transcriptionfactor that regulates a diverse array of cellular processes,including development, differentiation, proliferation, andapoptosis. Although its function in keratinocytes has beenwidely studied, its exact role in psoriasis has not beenelucidated. Objective: We designed this study to investigateepidermal expression levels of KLF4 and the change in KLF4expression after treatment in patients with psoriasis. Methods: We compared the expression levels of KLF4 in thebasal, suprabasal, and superficial epidermal layers, inpsoriatic lesional, non-lesional, and normal skin, using animmunoreactivity intensity distribution index (IRIDI). Inaddition, we measured the change in KLF4 expression on thebasis of the IRIDI and by reverse transcription polymerasechain reaction (RT-PCR) analysis after treatment. Results: Thecombined IRIDI scores in psoriatic lesional skin weresignificantly higher than the scores in both non-lesional andnormal skin. The psoriatic epidermis, particularly thesuprabasal layer, showed a significantly increased IRIDIscore compared to that of non-lesional and normal skin,which was significantly decreased after treatment. RT-PCRanalysis exhibited a slight increase in KLF4 mRNA expressionlevel after treatment; however, this increase was notsignificant. Conclusion: These data indicate that KLF4 couldregulate epidermal proliferation and differentiation. Moreover,we believe that KLF4 may play an important role in thephysiological reaction to counteract abnormal differentiationand proliferation of keratinocytes.
Abstract
Background: Krüppel-like factor 4 (KLF4) is a transcriptionfactor that regulates a diverse array of cellular processes,including development, differentiation, proliferation, andapoptosis. Although its function in keratinocytes has beenwidely studied, its exact role in psoriasis has not beenelucidated. Objective: We designed this study to investigateepidermal expression levels of KLF4 and the change in KLF4expression after treatment in patients with psoriasis. Methods: We compared the expression levels of KLF4 in thebasal, suprabasal, and superficial epidermal layers, inpsoriatic lesional, non-lesional, and normal skin, using animmunoreactivity intensity distribution index (IRIDI). Inaddition, we measured the change in KLF4 expression on thebasis of the IRIDI and by reverse transcription polymerasechain reaction (RT-PCR) analysis after treatment. Results: Thecombined IRIDI scores in psoriatic lesional skin weresignificantly higher than the scores in both non-lesional andnormal skin. The psoriatic epidermis, particularly thesuprabasal layer, showed a significantly increased IRIDIscore compared to that of non-lesional and normal skin,which was significantly decreased after treatment. RT-PCRanalysis exhibited a slight increase in KLF4 mRNA expressionlevel after treatment; however, this increase was notsignificant. Conclusion: These data indicate that KLF4 couldregulate epidermal proliferation and differentiation. Moreover,we believe that KLF4 may play an important role in thephysiological reaction to counteract abnormal differentiationand proliferation of keratinocytes.
참고문헌 (16)
- Kaczynski J, "Sp1- and Krüppel-like transcription factors", Genome Biol, 4, pp.206~ (2003)
- McConnell BB, "The diverse functions of Krüppel-like factors 4 and 5 in epithelial biology and pathobiology", Bioessays, 29, pp.549~557 (2007)
- Pearson R, "Krüppel-like transcription factors: a functional family", Int J Biochem Cell Biol, 40, pp.1996~2001 (2008)
- Garrett-Sinha LA, "A gene for a novel zinc-finger protein expressed in differentiated epithelial cells and transiently in certain mesenchymal cells", J Biol Chem, 271, pp.31384~31390 (1996)
- Shields JM, "Identification and characterization of a gene encoding a gut-enriched Krüppellike factor expressed during growth arrest", J Biol Chem, 271, pp.20009~20017 (1996)
- Conkright MD, "A gene encoding an intestinal-enriched member of the Krüppel-like factor family expressed in intestinal epithelial cells", Nucleic Acids Res, 27, pp.1263~1270 (1999)
- Segre JA, "Klf4 is a transcription factor required for establishing the barrier function of the skin", Nat Genet, 22, pp.356~360 (1999)
- Tsoi LC, "Identification of 15 new psoriasis susceptibility loci highlights the role of innate immunity", Nat Genet, 44, pp.1341~1348 (2012)
- Madonna S, "The IFN-gamma-dependent suppressor of cytokine signaling 1 promoter activity is positively regulated by IFN regulatory factor-1 and Sp1 but repressed by growth factor independence-1b and Krüppel-like factor-4, and it is dysregulated in psoriatic keratinocytes", J Immunol, 185, pp.2467~2481 (2010)
- Chaiyarit P, "Oral lichen planus: an immunohistochemical study of heat shock proteins (HSPs) and cytokeratins (CKs)and a unifying hypothesis of pathogenesis", J Oral Pathol Med, 28, pp.210~215 (1999)
- Jaubert J, "Ectopic expression of kruppel like factor 4 (Klf4) accelerates formation of the epidermal permeability barrier", Development, 130, pp.2767~2777 (2003)
- Chen X, "Transcriptional profiling of Krüppel-like factor 4 reveals a function in cell cycle regulation and epithelial differentiation", J Mol Biol, 326, pp.665~677 (2003)
- Chen X, "Krüppel-like factor 4 (gut-enriched Krüppellike factor) inhibits cell proliferation by blocking G1", S progression of the cell cycle, 2001, pp.276, 30423~30428
- Feinberg MW, "Kruppel-like factor 4 is a mediator of proinflammatory signaling in macrophages", J Biol Chem, 280, pp.38247~38258 (2005)
- Yamada T, "Transcription factor ELF4 controls the proliferation and homing of CD8+ T cells via the Krüppel-like factors KLF4 and KLF2", Nat Immunol, 10, pp.618~626 (2009)
- Rowland BD, "The KLF4 tumour suppressor is a transcriptional repressor of p53 that acts as a context-dependent oncogene", Nat Cell Biol, 7, pp.1074~1082 (2005)