STAT6-Dependent Collagen Synthesis in Human Fibroblasts Is Induced by Bovine Milk

Stefan Kippenberger; Nadja Zöller; Johannes Kleemann; Jutta Müller; Roland Kaufmann; Matthias Hofmann; August Bernd; Markus Meissner; Eva Valesky

doi:10.1371/journal.pone.0131783

STAT6-Dependent Collagen Synthesis in Human Fibroblasts Is Induced by Bovine Milk

PLoS One. 2015 Jul 2;10(7):e0131783. doi: 10.1371/journal.pone.0131783. eCollection 2015.

Authors

Stefan Kippenberger¹, Nadja Zöller¹, Johannes Kleemann¹, Jutta Müller¹, Roland Kaufmann¹, Matthias Hofmann¹, August Bernd¹, Markus Meissner¹, Eva Valesky¹

Affiliation

¹ Department of Dermatology, Venereology and Allergy, Johann Wolfgang Goethe University, Frankfurt/Main, Germany.

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adjuvants, Immunologic / chemistry
Animals
Cattle
Cell Membrane / metabolism
Cell Proliferation / drug effects
Collagen / biosynthesis*
Collagen Type I / biosynthesis
Fibroblasts / drug effects
Fibroblasts / metabolism*
Humans
Insulin / metabolism
Insulin-Like Growth Factor I / metabolism
Isoxazoles / chemistry
Leflunomide
Male
Milk / chemistry*
Mitogen-Activated Protein Kinase 1 / metabolism
Promoter Regions, Genetic
STAT6 Transcription Factor / metabolism*
Skin / drug effects
Skin / metabolism*
Transcription Factors / metabolism
Transcriptional Activation
p38 Mitogen-Activated Protein Kinases / metabolism

Substances

Adjuvants, Immunologic
Collagen Type I
Insulin
Isoxazoles
STAT6 Transcription Factor
STAT6 protein, human
Transcription Factors
WDR77 protein, human
Insulin-Like Growth Factor I
Collagen
Mitogen-Activated Protein Kinase 1
p38 Mitogen-Activated Protein Kinases
Leflunomide

Grants and funding

The study was supported by the Prof. Harry and Rosa Neumann-Stiftung and the Dr. Paul and Cilli Weil Stiftung (SK). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.