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Micellar Casein and Whey Powder Hold a TGF-β Activity and Regulate ID Genes In Vitro

Department of Oral Biology, Medical University of Vienna, Sensengasse 2a, 1090 Vienna, Austria
Department of Periodontology, School of Dental Medicine, University of Bern, Freiburgstrasse 7, 3010 Bern, Switzerland
Austrian Cluster for Tissue Regeneration, Donaueschingenstraße 13, 1200 Vienna, Austria
Author to whom correspondence should be addressed.
Academic Editor: Sokcheon Pak
Molecules 2021, 26(2), 507;
Received: 31 December 2020 / Revised: 13 January 2021 / Accepted: 14 January 2021 / Published: 19 January 2021
(This article belongs to the Special Issue Nutraceuticals in Immune Function)
Casein and whey being food supplements have been considered to be used in oral health care products. However, the response of oral cells to micellar casein and whey powder remains unclear. Considering that milk contains the growth factor TGF-β, and lactoperoxidase was recently reported to decrease the expression of inhibitor of DNA-binding (ID) proteins, there is a rationale to assume that casein and whey can also provoke these responses in oral cells. To examine the TGF-β activity, gingival fibroblasts were exposed to reconstituted casein and whey powder from food supplement before the expression of TGF-β target genes were analyzed by reverse transcription-quantitative polymerase chain reaction. Immunoassays were performed for interleukin11 (IL11) in the cell culture supernatant and for TGF-β in the reconstituted casein and whey. We blocked TGF-β by neutralizing the antibody and the TGF-β receptor type I kinase with the inhibitor SB431542. We also showed smad3 phosphorylation and smad2/3 nuclear translocation by Western blot and immunostaining, respectively. Moreover, with reconstituted casein and whey powder, ID1 and ID3 expression analysis was evaluated in HSC2 human oral squamous carcinoma cells. We report here that casein and whey powder caused a robust increase of TGF-β target genes interleukin11 (IL11), NADPH oxidase 4 (NOX4) and proteoglycan4 (PRG4) in gingival fibroblasts that was blocked by SB431542 and the neutralizing antibody. Moreover, casein and whey powder increased the phosphorylation of smad3 and nuclear translocation of smad2/3. No changes of proliferation markers Ki67 and cyclinD1 were observed. Furthermore, reconstituted casein and whey powder decreased ID1 and ID3 expression in the HSC2 oral squamous carcinoma cells. These findings suggest that the processing of milk into casein and whey powder maintains the TGF-β activity and its capacity to regulate ID1 and ID3 genes in oral fibroblasts and oral squamous carcinoma cells, respectively. These data increase the scientific knowledge on the biological activity of casein and whey with a special emphasis on oral health. View Full-Text
Keywords: casein; whey; TGF-β; fibroblasts; epithelial cells; oral health; nutrition casein; whey; TGF-β; fibroblasts; epithelial cells; oral health; nutrition
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MDPI and ACS Style

Panahipour, L.; Husejnovic, S.; Nasirzade, J.; Semelmayer, S.; Gruber, R. Micellar Casein and Whey Powder Hold a TGF-β Activity and Regulate ID Genes In Vitro. Molecules 2021, 26, 507.

AMA Style

Panahipour L, Husejnovic S, Nasirzade J, Semelmayer S, Gruber R. Micellar Casein and Whey Powder Hold a TGF-β Activity and Regulate ID Genes In Vitro. Molecules. 2021; 26(2):507.

Chicago/Turabian Style

Panahipour, Layla, Selma Husejnovic, Jila Nasirzade, Stephan Semelmayer, and Reinhard Gruber. 2021. "Micellar Casein and Whey Powder Hold a TGF-β Activity and Regulate ID Genes In Vitro" Molecules 26, no. 2: 507.

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