title: STAT6-Dependent Collagen Synthesis in Human Fibroblasts Is Induced by Bovine Milk.
abstract: Since the domestication of the urus, 10.000 years ago, mankind utilizes bovine milk for different purposes. Besides usage as a nutrient also the external application of milk on skin has a long tradition going back to at least the ancient Aegypt with Cleopatra VII as a great exponent. In order to test whether milk has impact on skin physiology, cultures of human skin fibroblasts were exposed to commercial bovine milk. Our data show significant induction of proliferation by milk (max. 2,3-fold, EC50: 2,5% milk) without toxic effects. Surprisingly, bovine milk was identified as strong inducer of collagen 1A1 synthesis at both, the protein (4-fold, EC50: 0,09% milk) and promoter level. Regarding the underlying molecular pathways, we show functional activation of STAT6 in a p44/42 and p38-dependent manner. More upstream, we identified IGF-1 and insulin as key factors responsible for milk-induced collagen synthesis. These findings show that bovine milk contains bioactive molecules that act on human skin cells. Therefore, it is tempting to test the herein introduced concept in treatment of atrophic skin conditions induced e.g. by UV light or corticosteroids.
authors.affiliation: Department of Dermatology, Venereology and Allergy, Johann Wolfgang Goethe University, Frankfurt/Main, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Kippenberger
authors.affiliation: Department of Dermatology, Venereology and Allergy, Johann Wolfgang Goethe University, Frankfurt/Main, Germany.
authors.forename: Nadja
authors.initials: N
authors.lastname: Zöller
authors.affiliation: Department of Dermatology, Venereology and Allergy, Johann Wolfgang Goethe University, Frankfurt/Main, Germany.
authors.forename: Johannes
authors.initials: J
authors.lastname: Kleemann
authors.affiliation: Department of Dermatology, Venereology and Allergy, Johann Wolfgang Goethe University, Frankfurt/Main, Germany.
authors.forename: Jutta
authors.initials: J
authors.lastname: Müller
authors.affiliation: Department of Dermatology, Venereology and Allergy, Johann Wolfgang Goethe University, Frankfurt/Main, Germany.
authors.forename: Roland
authors.initials: R
authors.lastname: Kaufmann
authors.affiliation: Department of Dermatology, Venereology and Allergy, Johann Wolfgang Goethe University, Frankfurt/Main, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Hofmann
authors.affiliation: Department of Dermatology, Venereology and Allergy, Johann Wolfgang Goethe University, Frankfurt/Main, Germany.
authors.forename: August
authors.initials: A
authors.lastname: Bernd
authors.affiliation: Department of Dermatology, Venereology and Allergy, Johann Wolfgang Goethe University, Frankfurt/Main, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Meissner
authors.affiliation: Department of Dermatology, Venereology and Allergy, Johann Wolfgang Goethe University, Frankfurt/Main, Germany.
authors.forename: Eva
authors.initials: E
authors.lastname: Valesky
mesh_terms: D000276:Adjuvants, Immunologic / Q000737:chemistry; D000818:Animals; D002417:Cattle; D002462:Cell Membrane / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D003094:Collagen / Q000096:biosynthesis*; D024042:Collagen Type I / Q000096:biosynthesis; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D007328:Insulin / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D007555:Isoxazoles / Q000737:chemistry; D000077339:Leflunomide; D008297:Male; D008892:Milk / Q000737:chemistry*; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D011401:Promoter Regions, Genetic; D050800:STAT6 Transcription Factor / Q000378:metabolism*; D012867:Skin / Q000187:drug effects / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism; D015533:Transcriptional Activation; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D000276:Adjuvants, Immunologic; D024042:Collagen Type I; D007328:Insulin; D007555:Isoxazoles; D050800:STAT6 Transcription Factor; C494101:STAT6 protein, human; D014157:Transcription Factors; C478359:WDR77 protein, human; D007334:Insulin-Like Growth Factor I; D003094:Collagen; D019950:Mitogen-Activated Protein Kinase 1; D048051:p38 Mitogen-Activated Protein Kinases; D000077339:Leflunomide