Keratinocyte growth factor induces hyperproliferation and delays differentiation in a skin equivalent model system
Open accessAbstract
Keratinocyte growth factor (KGF) is a paracrine mediator of epithelial cell growth. To examine the direct effects of KGF on the morphogenesis of the epidermis, we generated skin equivalents in vitro by seeding human keratinocytes on the papillary surface of acellular dermis and raising them up to the air‐liquid interface. KGF was either added exogenously or expressed by keratinocytes via a recombinant retrovirus encoding KGF. KGF induced dramatic changes to the 3‐dimensional organization of the epidermis including pronounced hyperthickening, crowding, and elongation of the basal cells, flattening of the rete ridges, and a ripple‐like pattern in the junction of stratum corneum and granular layers. Quantitative immunostaining for the proliferation antigen, Ki67, revealed that in addition to increasing basal proliferation, KGF extended the proliferative compartment by inducing suprabasal cell proliferation. KGF also induced expression of the integrin α5β1 and delayed expression of keratin 10 and transglutaminase. However, barrier formation of the epidermis was not disrupted. These results demonstrate for the first time that a single growth factor can alter the 3‐dimensional organization and proliferative function of an in vitro epidermis. In addition to new strategies for tissue engineering, such a well‐defined system will be useful for analyzing growth factor effects on the complex links between cell proliferation, cell movement and differentiation within a stratified tissue.—Andreadis, S. T., Hamoen, K. E., Yarmush, M. L., Morgan, J. R. Keratinocyte growth factor induces hyperproliferation and delays differentiation in a skin equivalent model system. FASEB J. 15, 898–909 (2001)
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
HSEs show marked molecular differences in basal and terminal gene expression, suggesting epidermal differentiation is not quite analogous to in vivo counterparts.
“Many studies defining HSEs have shown marked molecular differences in basal and terminal gene expression that suggest that epidermal differentiation is not quite analogous to the in vivo counterparts.”
From Single-cell transcriptomics of human-skin-equivalent organoids (2023) · cites this paper as [20]
The Discussion reports that KGF caused suprabasal proliferation in skin equivalents, whereas KGF-expressing mice showed no evidence of it. The ‘KGF delays differentiation’ section also reports altered differentiation-marker expression in KGF-treated equivalents versus control equivalents. These findings support a difference under KGF treatment, but not the broader claim that HSEs generally show marked basal and terminal gene-expression differences from in vivo epidermis. (LLM, conf=0.78)
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
No references could be resolved yet.
Research works printed but not linked: 4
- Miki, T., Bottaro, D. P., Fleming, T. P., Smith, C. L., Burgess, W. H., Chan, A. M., and Aaronson, S. A. (1992) Determination of ligand-binding specificity by alternative splicing: two distinct growth factor receptors encoded by a single gene. Proc. Natl. Acad. Sci. USA 89, 246 -250
- Werner, S., Peters, K. G., Longaker, M. T., Fuller-Pace, F., Banda, M. J., and Williams, L. T. (1992) Large induction of keratinocyte growth factor expression in the dermis during wound healing. Proc. Natl. Acad. Sci. USA 89, 6896 -6900
- Distante, F., and Berardesca, E. (1995) Hydration. In Bioengi- neering of the Skin: Methods and Instrumentation (Berardesca, E., Elsner, P., Wilhelm, K.-P., and Maibach, H. I., eds) pp. 5-12, CRC Press, Boca Raton, Florida
- Ohashi, T., Boggs, S., Robbins, P., Bahnson, A., Patrene, K., Wei, F. S., Wei, J. F., Li, J., Lucht, L., Fei, Y., et al. (1992) Efficient transfer and sustained high expression of the human glucoce- rebrosidase gene in mice and their functional macrophages following transplantation of bone marrow transduced by a retroviral vector. Proc. Natl. Acad. Sci. USA 89, 11332-11336
Cited by
Sorted by citations
Fibroblast heterogeneity: more than skin deep
Sorrell, J. M., & Caplan, A. I. (2004) · Journal of Cell Science · doi:10.1242/jcs.01005 · Cited by 553 · see citing works
Single-cell transcriptomics of human-skin-equivalent organoids
Stabell, A. R., Lee, G. E., Jia, Y., Wong, K. N., Wang, S., Ling, J., Nguyen, S. D., Sen, G. L., Nie, Q., & Atwood, S. X. (2023) · Cell Reports · doi:10.1016/j.celrep.2023.112511 · Cited by 30 · see citing works
- Authors
- Andreadis, S. T., Hamoen, K. E., Yarmush, M. L., & Morgan, J. R.
- Affiliations
- Center for Engineering in Medicine and Surgical Services, Massachusetts General Hospital Harvard Medical School and Shriners Burns Hospital Boston Massachusetts 02114 USA
- Harvard University (US)
- Venue
- The FASEB Journal
- Publisher
- Wiley
- Published
- 2001-04
- Volume
- 15
- Issue
- 6
- Pages
- 898-906
- ISSN
- 0892-6638 (ISSN-L)
- 1530-6860
- OpenAlex
- W2091841822
- Cited by
- 147
- References
- 0
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 1 · 2023: 1 · 2022: 3 · 2021: 6 · 2020: 1 · 2019: 4 · 2018: 3 · 2017: 3 · 2016: 4 · 2015: 4 · 2014: 4 · 2013: 11 · 2012: 6
- FWCI
- 4.52
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The FASEB Journal (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (HD-28528)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Skin and Cellular Biology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fibroblast Growth Factor Research
- Health Sciences › Medicine › Urology › Hair Growth and Disorders
- Keywords
- keratinocyte growth factor, epidermal hyperproliferation, keratinocyte differentiation, skin equivalents, epidermal morphogenesis, basal cell proliferation, alpha5beta1 integrin, keratin 10, transglutaminase, skin barrier function, air-liquid interface, tissue engineering
- MeSH terms
- Epidermal Cells, Cell Differentiation, Cell Division, Cells, Cultured, Epidermis, Fibroblast Growth Factors, Humans, Keratinocytes, Receptors, Fibronectin, Fibroblast Growth Factor 7
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
