Keratinocyte

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Micrograph of keratinocytes, basal cells and melanocytes in the epidermis Micrograph of keratinocytes, basal cells and melanocytes in the epidermis.jpg
Micrograph of keratinocytes, basal cells and melanocytes in the epidermis
Keratinocytes (stained green) in the skin of a mouse Proliferative response induced by a tumor promoter in the epidermis of a wild-type mouse - image.pbio.v11.i07.g001.png
Keratinocytes (stained green) in the skin of a mouse

Keratinocytes are the primary type of cell found in the epidermis, the outermost layer of the skin. In humans, they constitute 90% of epidermal skin cells. [1] Basal cells in the basal layer (stratum basale) of the skin are sometimes referred to as basal keratinocytes. [2] Keratinocytes form a barrier against environmental damage by heat, UV radiation, water loss, pathogenic bacteria, fungi, parasites, and viruses. A number of structural proteins, enzymes, lipids, and antimicrobial peptides contribute to maintain the important barrier function of the skin. Keratinocytes differentiate from epidermal stem cells in the lower part of the epidermis and migrate towards the surface, finally becoming corneocytes and eventually being shed, [3] [4] [5] [6] which happens every 40 to 56 days in humans. [7]

Contents

Function

The primary function of keratinocytes is the formation of a barrier against environmental damage by heat, UV radiation, dehydration, pathogenic bacteria, fungi, parasites, and viruses.

Pathogens invading the upper layers of the epidermis can cause keratinocytes to produce proinflammatory mediators, particularly chemokines such as CXCL10 and CCL2 (MCP-1) which attract monocytes, natural killer cells, T-lymphocytes, and dendritic cells to the site of pathogen invasion. [8]

Structure

A number of structural proteins (filaggrin, keratin), enzymes (e.g. proteases), lipids, and antimicrobial peptides (defensins) contribute to maintain the important barrier function of the skin. Keratinization is part of the physical barrier formation (cornification), in which the keratinocytes produce more and more keratin and undergo terminal differentiation. The fully cornified keratinocytes that form the outermost layer are constantly shed off and replaced by new cells. [3]

Cell differentiation

Epidermal stem cells reside in the lower part of the epidermis (stratum basale) and are attached to the basement membrane through hemidesmosomes. Epidermal stem cells divide in a random manner yielding either more stem cells or transit amplifying cells. [4] Some of the transit amplifying cells continue to proliferate then commit to differentiate and migrate towards the surface of the epidermis. Those stem cells and their differentiated progeny are organized into columns named epidermal proliferation units. [5]

During this differentiation process, keratinocytes permanently withdraw from the cell cycle, initiate expression of epidermal differentiation markers, and move suprabasally as they become part of the stratum spinosum, stratum granulosum, and eventually corneocytes in the stratum corneum.

Corneocytes are keratinocytes that have completed their differentiation program and have lost their nucleus and cytoplasmic organelles. [6] Corneocytes will eventually be shed off through desquamation as new ones come in.

At each stage of differentiation, keratinocytes express specific keratins, such as keratin 1, keratin 5, keratin 10, and keratin 14, but also other markers such as involucrin, loricrin, transglutaminase, filaggrin, and caspase 14.

In humans, it is estimated that keratinocytes turn over from stem cells to desquamation every 40–56 days, [7] whereas in mice the estimated turnover time is 8–10 days. [9]

Factors promoting keratinocyte differentiation are:

Since keratinocyte differentiation inhibits keratinocyte proliferation, factors that promote keratinocyte proliferation should be considered as preventing differentiation. These factors include:

Interaction with other cells

Within the epidermis keratinocytes are associated with other cell types such as melanocytes and Langerhans cells. Keratinocytes form tight junctions with the nerves of the skin and hold the Langerhans cells and intra-dermal lymphocytes in position within the epidermis. Keratinocytes also modulate the immune system: apart from the above-mentioned antimicrobial peptides and chemokines they are also potent producers of anti-inflammatory mediators such as IL-10 and TGF-β. When activated, they can stimulate cutaneous inflammation and Langerhans cell activation via TNFα and IL-1β secretion.[ citation needed ]

Keratinocytes contribute to protecting the body from ultraviolet radiation (UVR) by taking up melanosomes, vesicles containing the endogenous photoprotectant melanin, from epidermal melanocytes. Each melanocyte in the epidermis has several dendrites that stretch out to connect it with many keratinocytes. The melanin is then stored within keratinocytes and melanocytes in the perinuclear area as supranuclear “caps”, where it protects the DNA from UVR-induced damage. [28]

Role in wound healing

Wounds to the skin will be repaired in part by the migration of keratinocytes to fill in the gap created by the wound. The first set of keratinocytes to participate in that repair come from the bulge region of the hair follicle and will only survive transiently. Within the healed epidermis they will be replaced by keratinocytes originating from the epidermis. [29] [30]

At the opposite, epidermal keratinocytes, can contribute to de novo hair follicle formation during the healing of large wounds. [31]

Functional keratinocytes are needed for tympanic perforation healing. [32]

Sunburn cells

A sunburn cell is a keratinocyte with a pyknotic nucleus and eosinophilic cytoplasm that appears after exposure to UVC or UVB radiation or UVA in the presence of psoralens. It shows premature and abnormal keratinization, and has been described as an example of apoptosis. [33] [34]

Aging

With age, tissue homeostasis declines partly because stem/progenitor cells fail to self-renew or differentiate. DNA damage caused by exposure of stem/progenitor cells to reactive oxygen species (ROS) may play a key role in epidermal stem cell aging. Mitochondrial superoxide dismutase (SOD2) ordinarily protects against ROS. Loss of SOD2 in mouse epidermal cells was observed to cause cellular senescence that irreversibly arrested proliferation in a fraction of keratinocytes. [35] In older mice, SOD2 deficiency delayed wound closure and reduced epidermal thickness. [35]

Civatte body

Civatte body Civatte body.jpg
Civatte body

A Civatte body (named after the French dermatologist Achille Civatte, 1877–1956) [36] is a damaged basal keratinocyte that has undergone apoptosis, and consist largely of keratin intermediate filaments, and are almost invariably covered with immunoglobulins, mainly IgM. [37] Civatte bodies are characteristically found in skin lesions of various dermatoses, particularly lichen planus and discoid lupus erythematosus. [37] They may also be found in graft-versus-host disease, adverse drug reactions, inflammatory keratosis (such as lichenoid actinic keratosis and lichen planus-like keratosis), erythema multiforme, bullous pemphigoid, eczema, lichen planopilaris, febrile neutrophilic dermatosis, toxic epidermal necrolysis, herpes simplex and varicella zoster lesions, dermatitis herpetiformis, porphyria cutanea tarda, sarcoidosis, subcorneal pustular dermatosis, transient acantholytic dermatosis and epidermolytic hyperkeratosis. [37]

See also

Related Research Articles

<span class="mw-page-title-main">Skin</span> Soft outer covering organ of vertebrates

Skin is the layer of usually soft, flexible outer tissue covering the body of a vertebrate animal, with three main functions: protection, regulation, and sensation.

<span class="mw-page-title-main">Melanocyte</span> Melanin-producing cells of the skin

Melanocytes are melanin-producing neural crest-derived cells located in the bottom layer of the skin's epidermis, the middle layer of the eye, the inner ear, vaginal epithelium, meninges, bones, and heart. Melanin is a dark pigment primarily responsible for skin color. Once synthesized, melanin is contained in special organelles called melanosomes which can be transported to nearby keratinocytes to induce pigmentation. Thus darker skin tones have more melanosomes present than lighter skin tones. Functionally, melanin serves as protection against UV radiation. Melanocytes also have a role in the immune system.

<span class="mw-page-title-main">Integumentary system</span> Skin and other protective organs

The integumentary system is the set of organs forming the outermost layer of an animal's body. It comprises the skin and its appendages, which act as a physical barrier between the external environment and the internal environment that it serves to protect and maintain the body of the animal. Mainly it is the body's outer skin.

<span class="mw-page-title-main">Epidermis</span> Outermost of the three layers that make up the skin

The epidermis is the outermost of the three layers that comprise the skin, the inner layers being the dermis and hypodermis. The epidermis layer provides a barrier to infection from environmental pathogens and regulates the amount of water released from the body into the atmosphere through transepidermal water loss.

<span class="mw-page-title-main">Skin condition</span> Any medical condition that affects the integumentary system

A skin condition, also known as cutaneous condition, is any medical condition that affects the integumentary system—the organ system that encloses the body and includes skin, nails, and related muscle and glands. The major function of this system is as a barrier against the external environment.

<span class="mw-page-title-main">Stratum corneum</span> Outermost layer of the epidermis

The stratum corneum is the outermost layer of the epidermis. Consisting of dead tissue, it protects underlying tissue from infection, dehydration, chemicals and mechanical stress. It is composed of 15–20 layers of flattened cells with no nuclei and cell organelles.

<span class="mw-page-title-main">Keratin 1</span>

Keratin 1 is a Type II intermediate filament (IFs) of the intracytoplasmatic cytoskeleton. Is co-expressed with and binds to Keratin 10, a Type I keratin, to form a coiled coil heterotypic keratin chain. Keratin 1 and Keratin 10 are specifically expressed in the spinous and granular layers of the epidermis. In contrast, basal layer keratinocytes express little to no Keratin 1. Mutations in KRT1, the gene encoding Keratin 1, have been associated with variants of the disease bullous congenital ichthyosiform erythroderma in which the palms and soles of the feet are affected. Mutations in KRT10 have also been associated with bullous congenital ichthyosiform erythroderma; however, in patients with KRT10 mutations the palms and soles are spared. This difference is likely due to Keratin 9, rather than Keratin 10, being the major binding partner of Keratin 1 in acral keratinocytes.

<span class="mw-page-title-main">Stratum basale</span> Deepest layer of the five layers of the epidermis

The stratum basale is the deepest layer of the five layers of the epidermis, the external covering of skin in mammals.

<span class="mw-page-title-main">Hyperkeratosis</span> Medical condition

Hyperkeratosis is thickening of the stratum corneum, often associated with the presence of an abnormal quantity of keratin, and is usually accompanied by an increase in the granular layer. As the corneum layer normally varies greatly in thickness in different sites, some experience is needed to assess minor degrees of hyperkeratosis.

<span class="mw-page-title-main">Human skin</span> Organ covering the outside of the human body

The human skin is the outer covering of the body and is the largest organ of the integumentary system. The skin has up to seven layers of ectodermal tissue guarding muscles, bones, ligaments and internal organs. Human skin is similar to most of the other mammals' skin, and it is very similar to pig skin. Though nearly all human skin is covered with hair follicles, it can appear hairless. There are two general types of skin, hairy and glabrous skin (hairless). The adjective cutaneous literally means "of the skin".

<span class="mw-page-title-main">Hay–Wells syndrome</span> Medical condition

Hay–Wells syndrome is one of at least 150 known types of ectodermal dysplasia. These disorders affect tissues that arise from the ectodermal germ layer, such as skin, hair, and nails.

<span class="mw-page-title-main">TP63</span> Protein-coding gene in the species Homo sapiens

Tumor protein p63, typically referred to as p63, also known as transformation-related protein 63 is a protein that in humans is encoded by the TP63 gene.

Corneocytes are terminally differentiated keratinocytes and compose most of the stratum corneum, the outermost layer of the epidermis. They are regularly replaced through desquamation and renewal from lower epidermal layers and are essential for its function as a skin barrier.

Keratohyalin is a protein structure found in cytoplasmic granules of the keratinocytes in the stratum granulosum of the epidermis. Keratohyalin granules (KHG) mainly consist of keratin, profilaggrin, loricrin and trichohyalin proteins which contribute to cornification or keratinization, the process of the formation of epidermal cornified cell envelope. During the keratinocyte differentiation, these granules maturate and expand in size, which leads to the conversion of keratin tonofilaments into a homogenous keratin matrix, an important step in cornification.

<span class="mw-page-title-main">Involucrin</span> Protein-coding gene in the species Homo sapiens

Involucrin is a protein component of human skin and in humans is encoded by the IVL gene. In binding the protein loricrin, involucrin contributes to the formation of a cell envelope that protects corneocytes in the skin.

Skin sloughing is the process of shedding dead surface cells from the skin. It is most associated with cosmetic skin maintenance via exfoliation, but can also occur biologically or for medical reasons.

miR-203

In molecular biology miR-203 is a short non-coding RNA molecule. MicroRNAs function to regulate the expression levels of other genes by several mechanisms, such as translational repression and Argonaute-catalyzed messenger RNA cleavage. miR-203 has been identified as a skin-specific microRNA, and it forms an expression gradient that defines the boundary between proliferative epidermal basal progenitors and terminally differentiating suprabasal cells. It has also been found upregulated in psoriasis and differentially expressed in some types of cancer.

<span class="mw-page-title-main">LEKTI-2</span> Mammalian protein found in Homo sapiens

Lympho-epithelial Kazal-type related inhibitor 2 (LEKTI-2) is a protein encoded by the SPINK9 gene in humans. SPINK9 is a member of a gene family cluster located on chromosome 5q33.1, which includes SPINK5 and SPINK6. LEKTI-2 is an inhibitor of KLK5.

HaCaT is a spontaneously transformed aneuploid immortal keratinocyte cell line from adult human skin, widely used in scientific research. HaCaT cells are utilized for their high capacity to differentiate and proliferate in vitro. Their use in research allows for the characterization of human keratinocyte using a model that is reproducible and addresses issues such as short culture lifespan and variations between cell lines that would otherwise be encountered. These cells have allowed the characterization of several processes, such as their utilization as a model system for vitamin D3 metabolism in the skin.

<span class="mw-page-title-main">Topical cream formulation</span>

Topical cream formulation is an emulsion semisolid dosage form that is used for skin external application. Most of the topical cream formulations contain more than 20 per cent of water and volatiles and/or less than 50 per cent of hydrocarbons, waxes, or polyethylene glycols as the vehicle for external skin application. In a topical cream formulation, ingredients are dissolved or dispersed in either a water-in-oil (W/O) emulsion or an oil-in-water (O/W) emulsion. The topical cream formulation has a higher content of oily substance than gel, but a lower content of oily ingredient than ointment. Therefore, the viscosity of topical cream formulation lies between gel and ointment. The pharmacological effect of the topical cream formulation is confined to the skin surface or within the skin. Topical cream formulation penetrates through the skin by transcellular route, intercellular route, or trans-appendageal route. Topical cream formulation is used for a wide range of diseases and conditions, including atopic dermatitis (eczema), psoriasis, skin infection, acne, and wart. Excipients found in a topical cream formulation include thickeners, emulsifying agents, preservatives, antioxidants, and buffer agents. Steps required to manufacture a topical cream formulation include excipient dissolution, phase mixing, introduction of active substances, and homogenization of the product mixture.

References

  1. ↑ McGrath JA; Eady RAJ; Pope FM. (2004). "Anatomy and Organization of Human Skin". In Burns T; Breathnach S; Cox N; Griffiths C. (eds.). Rook's Textbook of Dermatology (7th ed.). Blackwell Publishing. p. 4190. doi:10.1002/9780470750520.ch3. ISBN   978-0-632-06429-8. Archived from the original on 2020-05-20. Retrieved 2010-06-01.
  2. ↑ James W, Berger T, Elston D (December 2005). Andrews' Diseases of the Skin: Clinical Dermatology (10th ed.). Saunders. pp. 5–6. ISBN   978-0-7216-2921-6. Archived from the original on 2010-10-11. Retrieved 2010-06-01.
  3. 1 2 Gilbert, Scott F. (2000). "The Epidermis and the Origin of Cutaneous Structures.". Developmental Biology . Sinauer Associates. ISBN   978-0878932436. Throughout life, the dead keratinized cells of the cornified layer are shed (humans lose about 1.5 grams of these cells each day*) and are replaced by new cells, the source of which is the mitotic cells of the Malpighian layer. Pigment cells (melanocytes) from the neural crest also reside in the Malpighian layer, where they transfer their pigment sacs (melanosomes) to the developing keratinocytes.
  4. 1 2 Houben E, De Paepe K, Rogiers V (2007). "A keratinocyte's course of life". Skin Pharmacology and Physiology. 20 (3): 122–32. doi:10.1159/000098163. PMID   17191035. S2CID   25671082.
  5. 1 2 Ghazizadeh S, Taichman LB (March 2001). "Multiple classes of stem cells in cutaneous epithelium: a lineage analysis of adult mouse skin". The EMBO Journal. 20 (6): 1215–22. doi:10.1093/emboj/20.6.1215. PMC   145528 . PMID   11250888.
  6. 1 2 Koster MI (July 2009). "Making an epidermis". Annals of the New York Academy of Sciences. 1170 (1): 7–10. Bibcode:2009NYASA1170....7K. doi:10.1111/j.1749-6632.2009.04363.x. PMC   2861991 . PMID   19686098.
  7. 1 2 Halprin KM (January 1972). "Epidermal "turnover time"--a re-examination". The British Journal of Dermatology. 86 (1): 14–9. doi:10.1111/j.1365-2133.1972.tb01886.x. PMID   4551262. S2CID   30165907.
  8. ↑ Murphy, Kenneth (Kenneth M.) (2017). Janeway's immunobiology. Weaver, Casey (Ninth ed.). New York, NY, USA. p. 112. ISBN   9780815345053. OCLC   933586700.{{cite book}}: CS1 maint: location missing publisher (link)
  9. ↑ Potten CS, Saffhill R, Maibach HI (September 1987). "Measurement of the transit time for cells through the epidermis and stratum corneum of the mouse and guinea-pig". Cell and Tissue Kinetics. 20 (5): 461–72. doi:10.1111/j.1365-2184.1987.tb01355.x. PMID   3450396. S2CID   22475141.
  10. ↑ Proksch E, Brandner JM, Jensen JM (December 2008). "The skin: an indispensable barrier". Experimental Dermatology. 17 (12): 1063–72. doi:10.1111/j.1600-0625.2008.00786.x. PMID   19043850. S2CID   31353914.
  11. ↑ Hennings H, Kruszewski FH, Yuspa SH, Tucker RW (April 1989). "Intracellular calcium alterations in response to increased external calcium in normal and neoplastic keratinocytes". Carcinogenesis. 10 (4): 777–80. doi:10.1093/carcin/10.4.777. PMID   2702726.
  12. ↑ Pillai S, Bikle DD (January 1991). "Role of intracellular-free calcium in the cornified envelope formation of keratinocytes: differences in the mode of action of extracellular calcium and 1,25 dihydroxyvitamin D3". Journal of Cellular Physiology. 146 (1): 94–100. doi:10.1002/jcp.1041460113. PMID   1990023. S2CID   21264605.
  13. ↑ Reiss, M; Lipsey, LR; Zhou, ZL (1991). "Extracellular calcium-dependent regulation of transmembrane calcium fluxes in murine keratinocytes". Journal of Cellular Physiology. 147 (2): 281–91. doi:10.1002/jcp.1041470213. PMID   1645742. S2CID   25858560.
  14. ↑ Mauro, TM; Pappone, PA; Isseroff, RR (1990). "Extracellular calcium affects the membrane currents of cultured human keratinocytes". Journal of Cellular Physiology. 143 (1): 13–20. doi:10.1002/jcp.1041430103. PMID   1690740. S2CID   8072916.
  15. ↑ Mauro, TM; Isseroff, RR; Lasarow, R; Pappone, PA (1993). "Ion channels are linked to differentiation in keratinocytes". The Journal of Membrane Biology. 132 (3): 201–9. doi:10.1007/BF00235738. PMID   7684087. S2CID   13063458.
  16. ↑ Tu, CL; Oda, Y; Bikle, DD (1999). "Effects of a calcium receptor activator on the cellular response to calcium in human keratinocytes". The Journal of Investigative Dermatology. 113 (3): 340–5. doi: 10.1046/j.1523-1747.1999.00698.x . PMID   10469331.
  17. ↑ Hennings, Henry; Michael, Delores; Cheng, Christina; Steinert, Peter; Holbrook, Karen; Yuspa, Stuart H. (1980). "Calcium regulation of growth and differentiation of mouse epidermal cells in culture". Cell. 19 (1): 245–54. doi:10.1016/0092-8674(80)90406-7. PMID   6153576. S2CID   23896865.
  18. ↑ Su, MJ; Bikle, DD; Mancianti, ML; Pillai, S (1994). "1,25-Dihydroxyvitamin D3 potentiates the keratinocyte response to calcium". The Journal of Biological Chemistry. 269 (20): 14723–9. doi: 10.1016/S0021-9258(17)36685-1 . PMID   7910167.
  19. ↑ Fu, G. K.; Lin, D; Zhang, MY; Bikle, DD; Shackleton, CH; Miller, WL; Portale, AA (1997). "Cloning of Human 25-Hydroxyvitamin D-1 -Hydroxylase and Mutations Causing Vitamin D-Dependent Rickets Type 1". Molecular Endocrinology. 11 (13): 1961–70. CiteSeerX   10.1.1.320.3485 . doi:10.1210/mend.11.13.0035. PMID   9415400.
  20. ↑ Kawakubo, Tomoyo; Yasukochi, Atsushi; Okamoto, Kuniaki; Okamoto, Yoshiko; Nakamura, Seiji; Yamamoto, Kenji (2011). "The role of cathepsin E in terminal differentiation of keratinocytes". Biological Chemistry. 392 (6): 571–85. doi:10.1515/BC.2011.060. hdl: 2324/25561 . PMID   21521076. S2CID   21148292.
  21. ↑ Jackson, B.; Brown, S. J.; Avilion, A. A.; O'Shaughnessy, R. F. L.; Sully, K.; Akinduro, O.; Murphy, M.; Cleary, M. L.; Byrne, C. (2011). "TALE homeodomain proteins regulate site-specific terminal differentiation, LCE genes and epidermal barrier". Journal of Cell Science. 124 (10): 1681–1690. doi:10.1242/jcs.077552. PMC   3183491 . PMID   21511732.
  22. 1 2 Rheinwald, JG; Green, H (1975). "Serial cultivation of strains of human epidermal keratinocytes: The formation of keratinizing colonies from single cells". Cell. 6 (3): 331–43. doi:10.1016/S0092-8674(75)80001-8. PMID   1052771. S2CID   53294766.
  23. ↑ Truong, AB; Kretz, M; Ridky, TW; Kimmel, R; Khavari, PA (2006). "P63 regulates proliferation and differentiation of developmentally mature keratinocytes". Genes & Development. 20 (22): 3185–97. doi:10.1101/gad.1463206. PMC   1635152 . PMID   17114587.
  24. ↑ Qu J, Tanis SE, Smits JP, Kouwenhoven EN, Oti M, van den Bogaard EH, Logie C, Stunnenberg HG, van Bokhoven H, Mulder KW, Zhou H (December 2018). "Mutant p63 affects epidermal cell identity through rewiring the enhancer landscape". Cell Reports. 25 (12): 3490–503. doi: 10.1016/j.celrep.2018.11.039 . hdl: 2066/200262 . PMID   30566872.
  25. ↑ Fuchs, E; Green, H (1981). "Regulation of terminal differentiation of cultured human keratinocytes by vitamin A". Cell. 25 (3): 617–25. doi:10.1016/0092-8674(81)90169-0. PMID   6169442. S2CID   23796587.
  26. ↑ Rheinwald, JG; Green, H (1977). "Epidermal growth factor and the multiplication of cultured human epidermal keratinocytes". Nature. 265 (5593): 421–4. Bibcode:1977Natur.265..421R. doi:10.1038/265421a0. PMID   299924. S2CID   27427541.
  27. ↑ Barrandon, Y; Green, H (1987). "Cell migration is essential for sustained growth of keratinocyte colonies: The roles of transforming growth factor-alpha and epidermal growth factor". Cell. 50 (7): 1131–7. doi:10.1016/0092-8674(87)90179-6. PMID   3497724. S2CID   21054962.
  28. ↑ Brenner M; Hearing VJ. (May–June 2008). "The Protective Role of Melanin Against UV Damage in Human Skin". Photochemistry and Photobiology . 84 (3): 539–549. doi:10.1111/j.1751-1097.2007.00226.x. PMC   2671032 . PMID   18435612.
  29. ↑ Ito, M; Liu, Y; Yang, Z; Nguyen, J; Liang, F; Morris, RJ; Cotsarelis, G (2005). "Stem cells in the hair follicle bulge contribute to wound repair but not to homeostasis of the epidermis". Nature Medicine. 11 (12): 1351–4. doi:10.1038/nm1328. PMID   16288281. S2CID   52869761.
  30. ↑ Claudinot, S; Nicolas, M; Oshima, H; Rochat, A; Barrandon, Y (2005). "Long-term renewal of hair follicles from clonogenic multipotent stem cells". Proceedings of the National Academy of Sciences of the United States of America. 102 (41): 14677–82. Bibcode:2005PNAS..10214677C. doi: 10.1073/pnas.0507250102 . PMC   1253596 . PMID   16203973.
  31. ↑ Ito, M; Yang, Z; Andl, T; Cui, C; Kim, N; Millar, SE; Cotsarelis, G (2007). "Wnt-dependent de novo hair follicle regeneration in adult mouse skin after wounding". Nature. 447 (7142): 316–20. Bibcode:2007Natur.447..316I. doi:10.1038/nature05766. PMID   17507982. S2CID   887738.
  32. ↑ Y Shen, Y Guo, C Du, M Wilczynska, S Hellström, T Ny, Mice Deficient in Urokinase-Type Plasminogen Activator Have Delayed Healing of Tympanic Membrane Perforations, PLOS ONE, 2012
  33. ↑ Young AR (June 1987). "The sunburn cell". Photodermatology . 4 (3): 127–134. PMID   3317295.
  34. ↑ Sheehan JM, Young AR (June 2002). "The sunburn cell revisited: an update on mechanistic aspects". Photochemical and Photobiological Sciences . 1 (6): 365–377. doi:10.1039/b108291d. PMID   12856704. S2CID   21184034.
  35. 1 2 Velarde MC, Demaria M, Melov S, Campisi J (August 2015). "Pleiotropic age-dependent effects of mitochondrial dysfunction on epidermal stem cells". Proc. Natl. Acad. Sci. U.S.A. 112 (33): 10407–12. Bibcode:2015PNAS..11210407V. doi: 10.1073/pnas.1505675112 . PMC   4547253 . PMID   26240345.
  36. ↑ Crissey, John Thorne; Parish, Lawrence C.; Holubar, Karl (2002). Historical Atlas of Dermatology and Dermatologists. Boca Raton, FL: CRC Press. p. 147. ISBN   1-84214-100-7.
  37. 1 2 3 Seema, Chhabra; Pranay, Tanwar; Kumar, AroraSandeep (2013). "Civatte bodies: A diagnostic clue". Indian Journal of Dermatology. 58 (4): 327. doi: 10.4103/0019-5154.113974 . ISSN   0019-5154. PMC   3726905 . PMID   23919028.
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