Unsaturated Fatty Acids Induce Calcium Influx into Keratinocytes and Cause Abnormal Differentiation of Epidermis  Yuji Katsuta, Toshii Iida, Shinji Inomata,

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Unsaturated Fatty Acids Induce Calcium Influx into Keratinocytes and Cause Abnormal Differentiation of Epidermis  Yuji Katsuta, Toshii Iida, Shinji Inomata, Mitsuhiro Denda  Journal of Investigative Dermatology  Volume 124, Issue 5, Pages 1008-1013 (May 2005) DOI: 10.1111/j.0022-202X.2005.23682.x Copyright © 2005 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 1 Topical application of unsaturated fatty acids induces scaly skin. (A) The untreated control is shown. Application of triolein did not affect skin surface morphology (B). Application of saturated acids, palmitic acid (C), or stearic acid (D) did not obviously affect the skin surface morphology. On the other hand, application of unsaturated fatty acids, palmitoleic acid (E), or oleic acid (F) induced scaly skin. Scale bar=1 mm. Journal of Investigative Dermatology 2005 124, 1008-1013DOI: (10.1111/j.0022-202X.2005.23682.x) Copyright © 2005 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 2 Parakeratosis of the epidermis was induced by topical application of unsaturated fatty acids. No nucleus was observed in keratinocytes of the control (A), triolein-treated skin (B), palmitic-acid-treated skin (C), and stearic-acid-treated skin (D). On the other hand, nuclei were observed in palmitoleic-acid-treated skin (E) and oleic-acid-treated skin (F). Results of quantification in each sample are shown in (G). *p<0.05, Scale bar=10 μm. Journal of Investigative Dermatology 2005 124, 1008-1013DOI: (10.1111/j.0022-202X.2005.23682.x) Copyright © 2005 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 3 Topical application of unsaturated fatty acids induced epidermal hyperplasia. Representative sections are shown in (A–F). (A) Control, (B) triolein, (C) palmitic acid, (D) stearic acid, (E) palmitoleic acid, (F) oleic acid. Results of quantification are shown in (G). *p<0.05. Scale bar=10 μm. Journal of Investigative Dermatology 2005 124, 1008-1013DOI: (10.1111/j.0022-202X.2005.23682.x) Copyright © 2005 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 4 Topical application of unsaturated fatty acids drastically increased transepidermal water loss. Topical application of triolein and free fatty acids increased transepidermal water loss (TEWL), and unsaturated fatty acids drastically increased the TEWL. Journal of Investigative Dermatology 2005 124, 1008-1013DOI: (10.1111/j.0022-202X.2005.23682.x) Copyright © 2005 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 5 Topical application of oleic acid induced abnormal loricrine expression. Immunoreactivity against anti-loricrin antiserum was observed in the uppermost layer of the epidermis of the skin from untreated mice (A) and triolein-treated mice (B). The region immunoreactive to anti-loricrin antiserum was broader in the epidermis from skin treated with oleic acid (C). Scale bar=10μm Journal of Investigative Dermatology 2005 124, 1008-1013DOI: (10.1111/j.0022-202X.2005.23682.x) Copyright © 2005 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 6 Application of unsaturated fatty acid increased the intracellular calcium concentration in cultured human keratinocytes. (A) A representative profile of intracellular calcium level after the application of oleic acid is shown. The results of quantification are shown in (B). *p<0.05. Journal of Investigative Dermatology 2005 124, 1008-1013DOI: (10.1111/j.0022-202X.2005.23682.x) Copyright © 2005 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 7 Topical application of oleic acid increased the calcium concentration in the uppermost layer of the epidermis. (A) The calcium profile of untreated skin is shown. A higher concentration of calcium is observed in the uppermost layer of the epidermis. (B) The calcium profile of the skin after application of oleic acid is shown. The region of higher calcium concentration becomes broader. Scale bar=10 μm. Journal of Investigative Dermatology 2005 124, 1008-1013DOI: (10.1111/j.0022-202X.2005.23682.x) Copyright © 2005 The Society for Investigative Dermatology, Inc Terms and Conditions