Enhancement of Collagen-I Levels in Human Gingival Fibroblasts by Small Molecule Activation of HIF-1α

Lucia Adriana Lifshits, Miryam Rabin, Ran Tohar, Francesca Netti, Matan Gabay, Marina Sova, Daniel Z. Bar, Evgeny Weinberg, Lihi Adler-Abramovich, Maayan Gal*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

2 Scopus citations


Collagen is the most abundant protein in various mammalian tissues and has an essential role in various cellular processes. Collagen is necessary for food-related biotechnological applications such as cultivated meat, medical engineering, and cosmetics. High-yield expression of natural collagen from mammalian cells is challenging and not cost-effective. Thus, external collagen is obtained primarily from animal tissues. Under cellular hypoxia, overactivation of the transcription factor hypoxia-inducible factor (HIF) was shown to correlate with enhanced accumulation of collagen. Herein, we showed that the small molecule ML228, a known molecular activator of HIF, enhances the accumulation of collagen type-I in human fibroblast cells. We report an increase in collagen levels by 2.33 ± 0.33 when fibroblasts were incubated with 5 μM of ML228. Our experimental results demonstrated, for the first time, that external modulation of the hypoxia biological pathway can boost collagen levels in mammalian cells. Our findings pave the way for enhancing natural collagen production in mammals by altering cellular signaling pathways.

Original languageEnglish
Pages (from-to)7829-7835
Number of pages7
JournalJournal of Agricultural and Food Chemistry
Issue number20
StatePublished - 24 May 2023


FundersFunder number
ADAMA Center in TAU
Ministry of Science, Technology and Space
Israel Science FoundationISF 632/20
Sackler Faculty of Medicine, Tel-Aviv University


    • collagen
    • extracellular matrix
    • fibroblasts
    • hypoxia
    • hypoxia-inducible factor (HIF)


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