Development, characterization, and wound healing of the keratin 14 promoted transforming growth factor-beta1 transgenic mouse - PubMed (original) (raw)
Development, characterization, and wound healing of the keratin 14 promoted transforming growth factor-beta1 transgenic mouse
Teddy Chan et al. Wound Repair Regen. 2002 May-Jun.
Abstract
Transforming growth factor-beta1 is a fibrogenic cytokine that is important in the development of fibroproliferative disorders of the skin after injury. To investigate the role of transforming growth factor-beta1 produced by keratinocytes during wound healing, a plasmid with the human transforming growth factor-beta1 gene coupled with the keratin 14 promoter (pG3Z: K14-TGF-beta1) was constructed. The construct was tested successfully in vitro before being used to generate transgenic animals, which were subsequently bred into homozygous and heterozygous lines. Genotype screening of founders and progeny was performed by Southern blotting and targeting of the transgene to the epidermis by the keratin 14 promoter was shown by reverse transcription polymerase chain reaction. The major phenotypic change observed in the transgenic animals was "scruffiness" of the fur attributed to transgene expression in the skin, seen primarily in the homozygous line. A significant reduction in the rate of reepithelialization of full-thickness excisional wounds of dorsal skin was seen in homozygous animals compared with normal litter-mate controls at day 7 (p < 0.05, Fisher's Exact test) and day 9 (p < 0.01) postwounding. Wounds in heterozygous animals also healed more slowly at day 9 (p < 0.01). Northern analysis of mRNA extracted from the wounds showed increased human transforming growth factor-beta1 message levels in homozygous and heterozygous animals, maximal at day 5. Significant increases in transforming growth factor-beta1 activity in healing wounds measured using the plasminogen activator inhibitor-1/luciferase assay were found in the transgenic strains at day 9 postinjury as compared with the normal litter-mate control mice (p < 0.001, ANOVA). Type I procollagen mRNA expression was higher in the homozygous and heterozygous animals, with the highest levels reached at day 9. By day 5 postwounding, biopsies of both homozygous and heterozygous tissues were significantly higher in collagen as compared with wounds in control animals (p < 0.05, ANOVA). Based on these data, the K14-TGF-beta1 transgenic mouse shows that excessive latent transforming growth factor-beta1 produced in the epidermal layer of the skin delays reepithelialization in excisional wounds but subsequently the cells of the epidermis stimulate dermal fibroblasts leading to fibrosis through a paracrine mechanism.
Similar articles
- Healing of burn wounds in transgenic mice overexpressing transforming growth factor-beta 1 in the epidermis.
Yang L, Chan T, Demare J, Iwashina T, Ghahary A, Scott PG, Tredget EE. Yang L, et al. Am J Pathol. 2001 Dec;159(6):2147-57. doi: 10.1016/s0002-9440(10)63066-0. Am J Pathol. 2001. PMID: 11733365 Free PMC article. - Genetically modified dermal keratinocytes express high levels of transforming growth factor-beta1.
Ghahary A, Tredget EE, Chang LJ, Scott PG, Shen Q. Ghahary A, et al. J Invest Dermatol. 1998 May;110(5):800-5. doi: 10.1038/jid.1998.5. J Invest Dermatol. 1998. PMID: 9579549 - Latent and active transforming growth factor beta1 released from genetically modified keratinocytes modulates extracellular matrix expression by dermal fibroblasts in a coculture system.
Bauer BS, Tredget EE, Marcoux Y, Scott PG, Ghahary A. Bauer BS, et al. J Invest Dermatol. 2002 Aug;119(2):456-63. doi: 10.1046/j.1523-1747.2002.01837.x. J Invest Dermatol. 2002. PMID: 12190870 - Role of TGF beta-mediated inflammation in cutaneous wound healing.
Wang XJ, Han G, Owens P, Siddiqui Y, Li AG. Wang XJ, et al. J Investig Dermatol Symp Proc. 2006 Sep;11(1):112-7. doi: 10.1038/sj.jidsymp.5650004. J Investig Dermatol Symp Proc. 2006. PMID: 17069018 Review.
Cited by
- The integrin αv-TGFβ signaling axis is necessary for epidermal proliferation during cutaneous wound healing.
Duperret EK, Natale CA, Monteleon C, Dahal A, Ridky TW. Duperret EK, et al. Cell Cycle. 2016 Aug 2;15(15):2077-86. doi: 10.1080/15384101.2016.1199306. Epub 2016 Jun 13. Cell Cycle. 2016. PMID: 27295308 Free PMC article. - Transforming Growth Factor Beta Signaling in Cutaneous Wound Healing: Lessons Learned from Animal Studies.
Finnson KW, Arany PR, Philip A. Finnson KW, et al. Adv Wound Care (New Rochelle). 2013 Jun;2(5):225-237. doi: 10.1089/wound.2012.0419. Adv Wound Care (New Rochelle). 2013. PMID: 24761336 Free PMC article. Review. - Chronic Wound Healing by Amniotic Membrane: TGF-β and EGF Signaling Modulation in Re-epithelialization.
Ruiz-Cañada C, Bernabé-García Á, Liarte S, Rodríguez-Valiente M, Nicolás FJ. Ruiz-Cañada C, et al. Front Bioeng Biotechnol. 2021 Jul 6;9:689328. doi: 10.3389/fbioe.2021.689328. eCollection 2021. Front Bioeng Biotechnol. 2021. PMID: 34295882 Free PMC article. Review. - Approaches for Regenerative Healing of Cutaneous Wound with an Emphasis on Strategies Activating the Wnt/β-Catenin Pathway.
Choi S, Yoon M, Choi KY. Choi S, et al. Adv Wound Care (New Rochelle). 2022 Feb;11(2):70-86. doi: 10.1089/wound.2020.1284. Epub 2021 Apr 20. Adv Wound Care (New Rochelle). 2022. PMID: 33573472 Free PMC article. - Proteomic identification of cyclophilin A as a potential biomarker and therapeutic target in oral submucous fibrosis.
Yuan Y, Hou X, Feng H, Liu R, Xu H, Gong W, Deng J, Sun C, Gao Y, Peng J, Wu Y, Li J, Fang C, Chen Q. Yuan Y, et al. Oncotarget. 2016 Sep 13;7(37):60348-60365. doi: 10.18632/oncotarget.11254. Oncotarget. 2016. PMID: 27533088 Free PMC article.
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Molecular Biology Databases
Miscellaneous