Article 14321

Title of the article

Intracellular mechanisms regulating the behavior of epidermal stem cells during skin regeneration (a review of literature) 

Authors

Tat'yana I. Vlasova, Doctor of medical sciences, associate professor, professor of the sub-department of normal and pathological physiology, Ogarev Mordovia State University (68 Bolshevistskaya street, Saransk, Russia), E-mail: v.t.i@bk.ru
Ekaterina V. Arsent'eva, Candidate of medical scinences, associate professor, associate professor of the sub-department of normal and pathological physiology, Ogarev Mordovia State University (68 Bolshevistskaya street, Saransk, Russia), E-mail: ev.arsenteva@yandex.ru
Bashir Abdulla Marzug, Student, Medical institute, Ogarev Mordovia State University (68 Bolshevistskaya street, Saransk, Russia), E-mail: inst-med@adm.mrsu.ru 

Index UDK

616-092.18 

DOI

10.21685/2072-3032-2021-3-14 

Abstract

Regenerative medicine is an extremely relevant and promising area of modern science, which can supplement theoretical knowledge about the mechanisms of epithelial regeneration and the main factors regulating this process. The article presents scientific studies devoted to the study of the molecular genetical mechanisms of the influence of epidermal stem cells on the wound healing and regeneration of the epithelium. The review includes data on the mechanisms of degree of expression integrins, keratin, a number of microRNAs and noncoding RNAs influence on the proliferation and differentiation of epithelial cells. The effects of microenvironment influence, in particular, Wnt and Notch signaling pathways, which are important components of stem cell microenvironment and play a significant role in skin formation and wound healing, are considered. It also contains information on the epigenetic regulation of the epidermal regeneration process. The mechanisms that realize the effects through interaction with PcG-active growth factor proteins and changes in the activity of histone demethylases, histone diacetylases, and DNA mithyltransferases are noted. The article contains modern ideas about ATP-dependent chromatin remodeling by proteins of the SNF2 family (including SWI2 / SNF2 (BRG1 / BRM), ISWI and CHD / Mi-2β), BRG1 and JMJD3 and their influence on differentiation and activity of epidermal stem cells. 

Key words

epidermal stem cells, integrin, keratin, microRNA, non-coding longchain RNAs, Wnt and Notch signaling pathways, epigenetic regulation of epidermal regeneration 

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References

1. Ronghua Y., Jingru W., Xiaodong Ch., Yan Sh., Julin X. Epidermal stem cells in wound healing and regeneration. 2020. Available at: https://www.hindawi.com/journals/sci/ 2020/9148310/ (accessed 14.10.2020).
2. Korbling M., Estrov Z. Adult stem cells for tissue repair – a new therapeutic concept? N. Engl. J. Med. 2003;6:570–582.
3. Xie L., Li T. Z., Qi S. H. [et al.]. A preliminary study on the identification and distribution of epidermal stem cells in different degrees of burn wounds in scalded rats. Zhonghua Shao Shang Za Zhi. 2003;6(19):344–346.
4. Eremina M.G., Eremin A.V., Eldesbaeva Ya.S., Drozdova S.B., Roshchepkina E.V., Chumachenko Yu.V. Regenerative capabilities of the skin. Saratovskiy nauchnomeditsinskiy zhurnal = Saratov scientific and medical journal. 2018;14(4):738–739. (In Russ.). Available at: https://cyberleninka.ru/article/n/regenerativnye-vozmozhnostikozhi (accessed 14.10.2020).
5. Rzepka K., Schaarschmidt G., Nagler M., Wohlrab J. Epidermalstemcells. Journal der Deutschen Dermatologischen Gesellschaft. 2005;12(3):962–973.
6. Chepurnenko M.N. Sources of post-traumatic regeneration of skin epithelium. Geny i kletki = Genes and cells. 2006;1(2):29–31. (In Russ.). Available at: https:// cyberleninka.ru/article/n/istochniki-posttravmaticheskoy-regeneratsii-epiteliya-kozhi/ viewer (accessed 14.10.2020).
7. Myadelets O.D., Lebedeva E.I., Myadelets N.Ya. Phosphatase-positive stem cells of rat skin during its post-traumatic regeneration under different conditions of wounding. Vestnik Vitebskogo gosudarstvennogo meditsinskogo universiteta = Bulletin of Vitebsk State Medical University. 2018;17(3):44–57. (In Russ.). Available at: https://cyberleninka.ru/article/n/fosfatazo-pozitivnye-stvolovye-kletki-kozhi-krys-priee- posttravmaticheskoy-regeneratsii-v-raznyh-usloviyah-naneseniya-rany/viewer (accessed 14.10.2020).
8. Pronina E.A., Maslyakov V.V., Stepanova T.V., Popykhova E.B., Ivanov A.N. Analysis of regeneration mechanisms during autotransplantation. Rossiyskiy medikobiologicheskiy vestnik imeni akademika I.P. Pavlova = The Russian medical and biological bulletin named after I. P. Pirogov. 2019;27(3):393–406. (In Russ.). Available at: https://cyberleninka.ru/article/n/analiz-mehanizmov-regeneratsii-pri-autotrasnlantatsii/ viewer (accessed 14.10.2020).
9. Blanpain C., Fuchs E. Epidermal homeostasis: a balancing act of stem cells in the skin. Nat Rev Mol Cell Biol. 2009;10(3):207–217.
10. Shibuya T., Honma M., Fujii M., Iinuma S. and Ishida-Yamamoto A. Podoplanin suppresses the cell adhesion of epidermal keratinocytes via functional regulation of β1-integrin. Archives of Dermatological Research. 2019;1(311):45–53.
11. Lechler T, Fuchs E. Asymmetric cell divisions promote stratification and differentiation of mammalian skin. Nature. 2005;8(437):275–280. doi:10.1038/nature03922
12. Jones P.H. and Watt F.M. Separation of human epidermal stem cells from transit amplifying cells on the basis of differences in integrin function and expression. Cell. 1993;4(73):713–724.
13. Zhan R., Wang F., Wu Y. [et al.]. Nitric oxide induces epidermal stem cell de-adhesion by targeting integrin β1 and Talin via the cGMP signalling pathway. Nitric Oxide. 2018;78:1–10.
14. Zhu J., Wang P., Yu Z. [et al.]. Advanced glycosylation end product promotes forkhead box O1 and inhibits Wnt pathway to suppress capacities of epidermal stem cells. American Journal of Translational Research. 2016;12(8):5569–5579.
15. Bai W.F., Xu W.C., Zhu H.X., Huang H., Wu B., Zhang M.S. Efficacy of 50 Hz electromagnetic fields on human epidermal stem cell transplantation seeded in collagen sponge scaffolds for wound healing in a murine model. Bioelectromagnetics. 2017;3(38):204–212.
16. Tanis S.E.J., Köksal E.S., van Buggenum J.A.G.L., Mulder K.W. BLNCR is a long non-coding RNA adjacent to integrin beta-1 that is rapidly lost during epidermal progenitor cell differentiation. Scientific Reports. 2019;1(9):31.
17. Rippa A.L.,Vorotelyak E., Vasiliev A.V., Terskikh V.V. The Role of Integrins in the Development and Homeostasis of the Epidermis and Skin Appendages. Acta naturae. 2013;5:22–33. doi:10.32607/20758251-2013-5-4-22-33
18. Zhou X., Li G., Wang D., Sun X., Li X. Cytokeratin expression in epidermal stem cells in skin adnexal tumors. Oncology Letters. 2019;1(17):927–932.
19. Nagosa S., Leesch F., Putin D. [et al.]. MicroRNA-184 induces a commitment switch to epidermal differentiation. Stem Cell Reports. 2017;6(9):1991–1994.
20. Spradling A., Drummond-Barbosa D., Kai T. Stem cells find their niche. Nature. 2001;414(6859):98–94.
21. Kretzschmar K., Clevers H. Wnt/β-catenin signaling in adult mammalian epithelial stem cells. Developmental Biology. 2017;2(428):273–282.
22. Sato M. Upregulation of the Wnt/β-catenin pathway induced by transforming growth Factor-β in hypertrophic scars and keloids. Acta Dermato-Venereologica. 2006;4(86):300–307.
23. Fre S., Huyghe M., Mourikis P., Robine S., Louvard D., and Artavanis-Tsakonas S. Notch signals control the fate of immature progenitor cells in the intestine. Nature. 2005;7044(435):964–968.
24. Zhang H., Nie X., Shi X. [et al.]. Regulatory mechanisms of the Wnt/β-Catenin pathway in diabetic cutaneous ulcers. Frontiers in Pharmacology. 2018;9:1114.
25. Xu G., Emmons R., Hernández-Saavedra D., Kriska A., Pan Y.X., and Chen H. Regulation of gene expression of wnt signaling pathway by dietary high fat and effects on colon epithelia of male mice. The FASEB Journal. 2017;31:622-43.
26. Nusse R. and Clevers H. Wnt/β-catenin signaling, disease, and emerging therapeutic modalities. Cell. 2017;6(169):985–999.
27. Huang P., Yan R., Zhang X., Wang L., Ke X. and Qu Y. Activating Wnt/β-catenin signaling pathway for disease therapy: challenges and opportunities. Pharmacology & Therapeutics. 2019;196:79–90.
28. McCubrey J.A., Rakus D., Gizak A. [et al.]. Effects of mutations in Wnt/β-catenin, hedgehog, Notch and PI3K pathways on GSK-3 activity—Diverse effects on cell growth, metabolism and cancer. Biochimica et Biophysica Acta (BBA) – Molecular Cell Research. 2016;12(1863):2942–2976.
29. Huelsken J., Vogel R., Erdmann B., Cotsarelis G., and Birchmeier W. β-catenin controls hair follicle morphogenesis and stem cell differentiation in the skin. Cell. 2001;4(105):533–545.
30. Choi Y.S., Zhang Y., Xu M. [et al.]. Distinct functions for Wnt/β-catenin in hair follicle stem cell proliferation and survival and interfollicular epidermal homeostasis. Cell. 2013;6(13):720–733.
31. Lim X., Tan S. H., Koh W. L. C. [et al.]. Interfollicular epidermal stem cells self-renew via autocrine Wnt signaling. Science. 2013;6163(342):1226–1230.
32. Niemann C., Owens D.M., Hulsken J., Birchmeier W. and Watt F. M. Expression of ΔNLef1 in mouse epidermis results in differentiation of hair follicles into squamous epidermal cysts and formation of skin tumours. Development. 2002;1(129):9–99.
33. Andl T., Reddy S.T., Gaddapara T. and Millar S.E. WNT signals are required for the initiation of hair follicle development. Developmental Cell. 2002;5(2):643–653.
34. Kretzschmar K., Cottle D.L., Schweiger P.J. and Watt F.M. The androgen receptor antagonizes Wnt/β-catenin signaling in epidermal stem cells. Journal of Investigative Dermatology. 2015;11(135):2753–2763.
35. Fathke C., Wilson L., Shah K. [et al.]. Wnt signaling induces epithelial differentiation during cutaneous wound healing. BMC Cell Biology. 2006;1(7):4.
36. Kopan R. Notch signaling. Cold Spring Harbor Perspectives in Biology. 2012;10(4):a011213.
37. Hori K., Sen A. and Artavanis-Tsakonas S. Notch signaling at a glance. Journal of Cell Science. 2013;126(10):2135–2140.
38. Varshney S. and Stanley P. Notch ligand binding assay using flow cytometry. Bio-Protocol. 2017;23(7):e2637.
39. Fiúza U., Arias A. Cell and molecular biology of Notch. Journal of Endocrinology. 2007;194(3):459–474.
40. Zhang R.Z., Zeng X.H., Lin Z.F. [et al.]. Downregulation of Hes1 expression in experimental biliary atresia and its effects on bile duct structure. World Journal of Gastroenterology. 2018;29(24):3260–3272.
41. Shi Y., Shu B., Yang R. [et al.]. Wnt and Notch signaling pathway involved in wound healing by targeting c-Myc and Hes1 separately. Stem Cell Research & Therapy. 2015;1(6):120.
42. Zeng F., Chen H., Zhang Z. [et al.]. Regulating glioma stem cells by hypoxia through the Notch1 and Oct3/4 signaling pathway. Oncology Letters. 2018;5(16):6315–6322.
43. Yi R. and Fuchs E. MicroRNA-mediated control in the skin. Cell Death & Differentiation. 2010;2(17):229–235.
44. Hildebrand J., Rütze M., Walz N. [et al.]. A comprehensive analysis of MicroRNA expression during human keratinocyte differentiation in vitro and in vivo. Journal of Investigative Dermatology. 2011;131(1):20–29.
45. Zhang L., Stokes N., Polak L., Fuchs E. Specific microRNAs are preferentially expressed by skin stem cells to balance self-renewal and early lineage commitment. Cell Stem Cell. 2011;8(3):294–298.
46. Lena A.M., Shalom-Feuerstein R., Rivetti di Val Cervo P., Aberdam D., Knight R.A., Melino G., Candi E. MiR-203 represses 'stemness' by repressing DeltaNp63. Cell Death Differ. 2008;15(7):1187–1195.
47. Viticchiè G., Lena A.M., Cianfarani F. [et al.]. MicroRNA-203 contributes to skin reepithelialization. Cell Death & Disease. 2012;3(11):e435.
48. Yi R., Poy M.N., Stoffel M., Fuchs E. A skin microRNA promotes differentiation by repressing 'stemness'. Nature. 2008;452(7184):225–229.
49. Koster M.I., Kim S., Mills A.A., DeMayo F., Roop D.R. p63 is the molecular switch for initiation of an epithelial stratification program. Genes & Development. 2004;18(2):126–131.
50. Pastar I., Khan A.A., Stojadinovic O. [et al.]. Induction of specific microRNAs inhibits cutaneous wound healing. Journal of Biological Chemistry. 2012;287(35):29324–2935.
51. Michel M., L'Heureux N., Auger F.A. and Germain L. From newborn to adult: phenotypic and functional properties of skin equivalent and human skin as a function of donor age. Journal of Cellular Physiology. 1997;2(171):179–189.
52. Hu W., Alvarez-Dominguez J.R., Lodish H.F. Regulation of mammalian cell differentiation by long non-coding RNAs. EMBO Reports. 2012;13(11):971–983.
53. Kretz M, Siprashvili Z, Chu C, Webster D.E., Zehnder A., Qu K., Lee C.S., Flockhart R.J., Groff A.F., Chow J., Johnston D., Kim G.E., Spitale R.C., Flynn R.A., Zheng G.X., Aiyer S., Raj A., Rinn J.L., Chang H.Y., Khavari P.A. Suppression of progenitor differentiation requires the long noncoding RNA ANCR. Genes Dev. 2012;26:338–343.
54. Kretz M., Siprashvili Z., Chu C., Webster D.E., Zehnder A., Qu K., Lee C.S., Flockhart R.J., Groff A.F., Chow J., Johnston D., Kim G.E., Spitale R.C., Flynn R.A., Zheng G.X., Aiyer S., Raj A., Rinn J.L., Chang H.Y., Khavari P.A. Control of somatic tissue differentiation by the long non-coding RNA TINCR. Nature. 2013;493(7431):231–235.
55. Lopez-Pajares V., Qu K., Zhang J. [et al.]. A LncRNA-MAF:MAFB transcription factor network regulates epidermal differentiation. Dev Cell. 2015;32(6):693–706. doi:10.1016/j.devcel.2015.01.028
56. Ziegler C., Graf J., Faderl S., Schedlbauer J., Strieder N., Förstl B., Spang R., Bruckmann A., Merkl R., Hombach S., Kretz M. The long non-coding RNA LINC00941 and SPRR5 are novel regulators of human epidermal homeostasis. EMBO Rep. 2019;(2):e46612. doi:10.15252/embr.201846612
57. Shi Y, Yang R, Tu L, Liu D. Long non‑coding RNA HOTAIR promotes burn wound healing by regulating epidermal stem cells. Mol Med Rep. 2020;(3):1811–1820. doi:10.3892/mmr.2020.11268
58. Shaw T., Martin P. Epigenetic reprogramming during wound healing: loss of polycombmediated silencing may enable upregulation of repair genes. EMBO Rep. 2009;10(8):881–886.
59. Mardaryev A.N. Epigenetic Regulation of Skin Wound Healing. Epigenetic Regulation of Skin Development and Regeneration: Stem Cell Biology and Regenerative Medicine 1st ed. Canada, 2018:293.
60. Ganguli-Indra G. and Indra A.K. The Role of ATP-dependent Chromatin Remodeling in the Control of Epidermal Differentiation and Skin Stem Cell Activity. Epigenetic Regulation of Skin Development and Regeneration: Stem Cell Biology and Regenerative Medicine. 2018:159.
61. Shaw T, Martin P. Epigenetic reprogramming during wound healing: loss of polycombmediated silencing may enable upregulation of repair genes. EMBO Rep. 2009;10(8):881–886.
62. Silina E.V., Manturova N.E., Artyushkova E.B., Litvitskiy P.F., Vasin V.I., Sinel'nikova T.G., Gladchenko M.P., Kryukov A.A., Anikanov A.V., Kaplin A., Naimzada M., Stupin V. The dynamics of skin wound healing with the use of injection stimulators of regeneration in rats. Patologicheskaya fiziologiya i eksperimental'naya terapiya = Pathological physiology and experimental therapy. 2020;64(3):54–63. (In Russ.)
63. Indra A.K., Li M., Brocard J., Warot X., Bornert J.M., Gerard C., Messaddeq N., Chambon P., Metzger D. Targeted somatic mutagenesis in mouse epidermis. Horm Res. 2000;54(5–6):296–300.
64. Indra A.K., Warot X., Brocard J., Bornert J.M., Xiao J.H., Chambon P., Metzger D. Temporallycontrolled site-specific mutagenesis in the basal layer of the epidermis: comparison of the recombinase activity of the tamoxifen-inducible Cre-ER(T) and Cre-ER(T2) recombinases. Nucleic Acids Res. 1999;27(22):4324–4327.
65. Metzger D., Indra A.K., Li M., Chapellier B., Calleja C., Ghyselinck N.B., Chambon P. Targeted conditional somatic mutagenesis in the mouse: temporally-controlled knock out of retinoid receptors in epidermal keratinocytes. Methods Enzymol. 2003;364:379–380.

 

Дата создания: 23.11.2021 14:21
Дата обновления: 25.11.2021 13:36