Selective Ablation of BCL11A in Epidermal Keratinocytes Alters Skin Homeostasis and Accelerates Excisional Wound Healing In Vivo

Overview

Journal Cells

Publisher MDPI

Specialties Biochemistry
Biophysics
Cell Biology
Molecular Biology

Date 2022 Jul 9

PMID 35805190

Authors

Nilika Bhattacharya

Arup K Indra

Gitali Ganguli-Indra

Affiliations

Soon will be listed here.

Abstract

Transcriptional regulator BCL11A plays a crucial role in coordinating a suite of developmental processes including skin morphogenesis, barrier functions and lipid metabolism. There is little or no reports so far documenting the role of BCL11A in postnatal adult skin homeostasis and in the physiological process of tissue repair and regeneration. The current study establishes for the first time the In Vivo role of epidermal BCL11A in maintaining adult epidermal homeostasis and as a negative regulator of cutaneous wound healing. Conditional ablation of in skin epidermal keratinocytes (mice) enhances the keratinocyte proliferation and differentiation program, suggesting its critical role in epidermal homeostasis of adult murine skin. Further, loss of keratinocytic BCL11A promotes rapid closure of excisional wounds both in a cell autonomous manner likely via accelerating wound re-epithelialization and in a non-cell autonomous manner by enhancing angiogenesis. The epidermis specific knockout mouse serves as a prototype to gain mechanistic understanding of various downstream pathways converging towards the manifestation of an accelerated healing phenotype upon its deletion.

Citing Articles

eIF6 modulates skin wound healing by upregulating keratin 6B.

Wang X, Xu G, Zhang F, Wei Y, Deng J, Mu L Stem Cells Transl Med. 2024; 13(11):1101-1112.

PMID: 39406496 PMC: 11555475. DOI: 10.1093/stcltm/szae064.

Metabolic characteristics of granulosa cell tumor: role of PPARγ signaling†.

Yu S, Luan Y, Xu P, Zhang Y, Dong R, Abazarikia A Biol Reprod. 2023; 110(3):509-520.

PMID: 38123510 PMC: 10941086. DOI: 10.1093/biolre/ioad173.

Retinoic Acid and Retinoid X Receptors.

Schubert M, Germain P Cells. 2023; 12(6).

PMID: 36980205 PMC: 10047840. DOI: 10.3390/cells12060864.

References

Li B, Wang J . Fibroblasts and myofibroblasts in wound healing: force generation and measurement. J Tissue Viability. 2009; 20(4):108-20. PMC: 2891362. DOI: 10.1016/j.jtv.2009.11.004. View

Zomer H, Trentin A . Skin wound healing in humans and mice: Challenges in translational research. J Dermatol Sci. 2018; 90(1):3-12. DOI: 10.1016/j.jdermsci.2017.12.009. View

Pastar I, Stojadinovic O, Yin N, Ramirez H, Nusbaum A, Sawaya A . Epithelialization in Wound Healing: A Comprehensive Review. Adv Wound Care (New Rochelle). 2014; 3(7):445-464. PMC: 4086220. DOI: 10.1089/wound.2013.0473. View

Alonso L, Fuchs E . Stem cells of the skin epithelium. Proc Natl Acad Sci U S A. 2003; 100 Suppl 1:11830-5. PMC: 304094. DOI: 10.1073/pnas.1734203100. View

Li S, Fang X, Wang X, Fei B . Fos-like antigen 2 (FOSL2) promotes metastasis in colon cancer. Exp Cell Res. 2018; 373(1-2):57-61. DOI: 10.1016/j.yexcr.2018.08.016. View

Volksdorf T, Heilmann J, Eming S, Schawjinski K, Zorn-Kruppa M, Ueck C . Tight Junction Proteins Claudin-1 and Occludin Are Important for Cutaneous Wound Healing. Am J Pathol. 2017; 187(6):1301-1312. DOI: 10.1016/j.ajpath.2017.02.006. View

Zhou J, Zhou L, Zhang D, Tang W, Tang D, Shi X . BCL11A Promotes the Progression of Laryngeal Squamous Cell Carcinoma. Front Oncol. 2020; 10:375. PMC: 7098986. DOI: 10.3389/fonc.2020.00375. View

Bhattacharya S, Wheeler H, Leid M, Ganguli-Indra G, Indra A . Transcription Factor CTIP2 Maintains Hair Follicle Stem Cell Pool and Contributes to Altered Expression of LHX2 and NFATC1. J Invest Dermatol. 2015; 135(11):2593-2602. PMC: 4640969. DOI: 10.1038/jid.2015.281. View

Haensel D, Jin S, Sun P, Cinco R, Dragan M, Nguyen Q . Defining Epidermal Basal Cell States during Skin Homeostasis and Wound Healing Using Single-Cell Transcriptomics. Cell Rep. 2020; 30(11):3932-3947.e6. PMC: 7218802. DOI: 10.1016/j.celrep.2020.02.091. View

10.

Gerritsen M, Elbers M, de Jong E, van de Kerkhof P . Recruitment of cycling epidermal cells and expression of filaggrin, involucrin and tenascin in the margin of the active psoriatic plaque, in the uninvolved skin of psoriatic patients and in the normal healthy skin. J Dermatol Sci. 1997; 14(3):179-88. DOI: 10.1016/s0923-1811(96)00570-1. View

11.

Wurm S, Zhang J, Guinea-Viniegra J, Garcia F, Munoz J, Bakiri L . Terminal epidermal differentiation is regulated by the interaction of Fra-2/AP-1 with Ezh2 and ERK1/2. Genes Dev. 2014; 29(2):144-56. PMC: 4298134. DOI: 10.1101/gad.249748.114. View

12.

Luo S, Yufit T, Carson P, Fiore D, Falanga J, Lin X . Differential keratin expression during epiboly in a wound model of bioengineered skin and in human chronic wounds. Int J Low Extrem Wounds. 2011; 10(3):122-9. PMC: 4082561. DOI: 10.1177/1534734611418157. View

13.

Rhim J, Jang I, Kwon S, Song K, Yeo E, Park S . Activation of wound healing in aged rats by altering the cellular mitogenic potential. J Gerontol A Biol Sci Med Sci. 2010; 65(7):704-11. DOI: 10.1093/gerona/glq065. View

14.

Berumen Sanchez G, Bunn K, Pua H, Rafat M . Extracellular vesicles: mediators of intercellular communication in tissue injury and disease. Cell Commun Signal. 2021; 19(1):104. PMC: 8520651. DOI: 10.1186/s12964-021-00787-y. View

15.

Vagnozzi A, Reiter J, Wong S . Hair follicle and interfollicular epidermal stem cells make varying contributions to wound regeneration. Cell Cycle. 2015; 14(21):3408-17. PMC: 4825603. DOI: 10.1080/15384101.2015.1090062. View

16.

Nejati R, Kovacic D, Slominski A . Neuro-immune-endocrine functions of the skin: an overview. Expert Rev Dermatol. 2014; 8(6):581-583. PMC: 3938165. DOI: 10.1586/17469872.2013.856690. View

17.

Leigh I, Navsaria H, Purkis P, McKay I, Bowden P, Riddle P . Keratins (K16 and K17) as markers of keratinocyte hyperproliferation in psoriasis in vivo and in vitro. Br J Dermatol. 1995; 133(4):501-11. DOI: 10.1111/j.1365-2133.1995.tb02696.x. View

18.

Gorell E, Nguyen N, Lane A, Siprashvili Z . Gene therapy for skin diseases. Cold Spring Harb Perspect Med. 2014; 4(4):a015149. PMC: 3968787. DOI: 10.1101/cshperspect.a015149. View

19.

Li S, Teegarden A, Bauer E, Choi J, Messaddeq N, Hendrix D . Transcription Factor CTIP1/ BCL11A Regulates Epidermal Differentiation and Lipid Metabolism During Skin Development. Sci Rep. 2017; 7(1):13427. PMC: 5647389. DOI: 10.1038/s41598-017-13347-7. View

20.

Rakita A, Nikolic N, Mildner M, Matiasek J, Elbe-Burger A . Re-epithelialization and immune cell behaviour in an ex vivo human skin model. Sci Rep. 2020; 10(1):1. PMC: 6959339. DOI: 10.1038/s41598-019-56847-4. View