Hair keratin

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Hair keratin is a type of keratin found in hair and the nails.

Contents

Function

Originating from the embryonic epidermis, the hair follicle evolves into one of the most complex structures in the human body, comprising 7–8 distinct tissue sections. [1] The base of the hair follicle contains the bulb, housing dermal fibroblasts known as the dermal papilla, crucial for morphogenesis and the hair follicle's cyclic activity. Encircling these cells is the matrix cell region, the hair follicle's proliferative compartment, responsible for the formation of different follicle compartments (except the ORS) and the production of crucial structural elements of hair - hair keratins and associated proteins known as KAPs. [1]

Keratin is a crucial fibrous protein found in animals, constituting tough structures like hair, feathers, nails, and horns. It's classified based on tissue origin and sulfur content: soft keratins have lower sulfur, while hard keratins, found in hair and claws, contain more sulfur, creating a stronger structure. [2] Keratins belong to two types - acidic Type I and neutral-basic Type II, further categorized into Type I a and b, and Type II a and b. The initial step in forming keratin is the alignment of type I and type II keratin polypeptides to create a heterodimer, which then aggregates into higher-order structural units. [2] Similar to other intermediate filament subunit proteins, a prevalent secondary structure exists: a well-preserved, central alpha-helical domain made up of four coiled-coil segments along with non-helical end-terminal domains that vary in sequences and lengths [14]. Recent findings suggest that the interaction between acidic and basic soft keratins initiates with the creation of a heterodimer. This heterodimer comprises an acidic and a basic monomeric keratin. Two of these heterodimers then combine to form a tetramer, which subsequently polymerizes, resulting in the formation of the final 10-nanometer filamentous structure. [3]

Stability

Due to their role as structural stabilizers in epithelial cells, keratin filaments have garnered significant interest across biology, embryology, pathology, and dermatology. This fundamental cytoskeletal function extends beyond individual cell levels. Typically, keratin filaments are integrated into desmosomes (see Fig. 1b, d) and hemidesmosomes, contributing not only to cell-to-cell stability but also to the attachment to the basement membrane and the connective tissue within a particular epithelium. [4] In non-stratified (simple) epithelia of internal organs experiencing minimal mechanical stress, only a few keratin types form sparsely distributed filaments within the cytoplasm. However, a more substantial number of keratin types participate in the intermediate filament cytoskeletal framework of squamous epithelia, which becomes more prominent in cornified stratified epithelia like the epidermis covering the body's outer surface. Here, keratins are abundant and densely packed, forming tonofilaments. [4]

Wound Healing

Recent attention has been drawn to the remarkable wound-healing capabilities and excellent biocompatibility of keratin derived from human hair. While recombinant keratin proteins produced via recombinant DNA technology offer higher purity compared to extracted keratin, their wound-healing properties have remained unclear. Two recombinant trichocyte keratins—human type I hair keratin 37 and human type II hair keratin 81—were expressed using a bacterial expression system and subsequently forming recombinant keratin nanoparticles (RKNPs) through ultrasonic dispersion. [5] It has been revealed that RKNPs significantly boosted cell proliferation and migration in laboratory settings. Moreover, when applied to dermal wounds in vivo, RKNPs facilitated improved wound healing, leading to enhanced epithelialization, vascularization, collagen deposition, and remodeling. Importantly, tests for in vivo biocompatibility showed no signs of systemic toxicity.  RKNPs have potential as a promising approach for advancing wound healing and suggests new avenues for developing keratin-based biomaterials. [5]

Reduced Bleeding

In vivo haemostasis efficacy studies were conducted using rat models of liver puncture and femoral artery injury. For both models, K37 and K81 (10 mg) were applied to cover the wound areas. In the liver puncture model, bleeding time significantly decreased with recombinant K37 (approximately 38 s) and K81 (approximately 40 s) compared to the vehicle alone (approximately 170 s, p < .01), with notably reduced total blood loss (p < .01). [6] Furthermore, in the femoral artery injury model, the recombinant keratin proteins significantly reduced bleeding time compared to the control group (approximately 50 s vs. 270 s). Notably, K37 and K81 exhibited stronger haemostatic effects than extracted keratins (approximately 80 s) in treating rat liver injury.  Additionally, the recombinant keratin proteins demonstrated a robust capacity to promote the formation of a fibrin clot at the injury site, effectively stopping the bleeding. Consequently, recombinant human hair keratins offer potential for developing novel haemostatic products based on keratin biomaterials. [6]

Types

There are two types of hair keratin:

Associated proteins

The arrangement of hair's layers--the cortex and cuticle--forms a hierarchical structure. The cortex primarily consists of a keratin coiled-coil protein phase. These proteins assemble into intermediate filaments, progressively forming larger fibers. Enveloping the hair is the cuticle, composed of deceased cells. X-ray data from various samples consistently reveal specific signals associated with the coiled-coil keratin phase, intermediate filament development in the cortex, and the cell membrane complex. The figure demonstrates signal assignments and their respective length scales. Hierarchical structure of hair in the cortex and cuticle.png
The arrangement of hair's layers—the cortex and cuticle—forms a hierarchical structure. The cortex primarily consists of a keratin coiled-coil protein phase. These proteins assemble into intermediate filaments, progressively forming larger fibers. Enveloping the hair is the cuticle, composed of deceased cells. X-ray data from various samples consistently reveal specific signals associated with the coiled-coil keratin phase, intermediate filament development in the cortex, and the cell membrane complex. The figure demonstrates signal assignments and their respective length scales.

The hair shaft is majorly composed of hair keratins and their associated proteins (KRTAPs). KRTAPs are products of diverse gene families resulting from gene duplication events in their evolutionary history. These genes are typically small, comprising a single exon less than 1,000 base pairs long. Over the last decade, numerous KRTAP genes have been identified across mammals, including humans. They are categorized into three groups based on their amino acid composition: high sulfur (with <30 mol% cysteine), ultrahigh sulfur (>30 mol% cysteine), and high glycine/tyrosine. [7] Hair keratins form intermediate filaments (KIFs) within trichocytes, specialized cells that contribute to hair formation. As these cells move upward in the cortex, KIFs aggregate, surrounded by a space called the matrix. KRTAPs, also known as KAPs, are a significant part of this matrix between KIFs. It's suggested that KRTAPs play a role in establishing a cross-linked network with KIFs, contributing to the creation of the rigid hair shaft. [7]

Gene expression

During hair growth, as follicle bulb cells swiftly transform into cortical or cuticle hair keratinocytes, approximately 50-100 keratin genes become activated at the transcriptional level. [8] However, this intricate process can be simplified into a few highly preserved gene families. In cortical keratinocytes, distinct patterns of keratin gene expression are evident, indicating the presence of different hierarchical transcription processes among various cell types. Examination of keratin gene promoter regions reveals conserved sequence motifs that might govern these cell-specific traits. [8] Moreover, through the isolation of related sheep and human cuticle keratin genes, conserved DNA motifs and expression patterns during cuticle cell differentiation have been discovered. Further, the expression of sheep wool follicle IF and high-sulfur keratin genes in transgenic mice suggests that the regulatory DNA elements and proteins associated with hair keratin genes maintain functional conservation across mammalian species. [8]

Clinical significance

Breast cancer

Keratin constitutes a large multigene family known as cytokeratins. These cytokeratins are differentially expressed across various epithelial types and have been extensively studied as markers for breast cancer. They are categorized into acidic type I and basic-to-neutral type II cytokeratins. [9] The intermediate filament network is formed by the necessary pairing of equal amounts of type I and type II keratins. While hair keratins, such as KRT81, are typical in hard-keratinized structures like hair and nails, they are thought to serve as structural proteins specific to these organs without expression elsewhere, such as the mammary gland.

KRT81, a type II hair keratin, is a major hair protein expressed in the hair cortex. Interestingly, despite being typically associated with hair structures, KRT81 expression has been observed in the SKBR3 human breast cancer cell line and metastatic lymph nodes of breast carcinomas, but not in normal breast epithelial cells. Moreover, the expressed KRT81 was found to be a 5′-truncated isoform (ΔHb1), with the full-length protein not being expressed. [9] However, the exact function of this truncated form in breast cancer cells remains unclear.

Western blot analysis detected the presence of the complete 55-kDa KRT81 in various human breast cancer cell lines (MCF7, SKBR3, MDA-MB-231), normal human mammary epithelial cells (HMEC), and non-neoplastic cells (MCF10A). [9]  Reverse transcription-polymerase chain reaction confirmed the expression of the full-length KRT81, encompassing its 5' region, in breast cells. Immunohistochemical and immunofluorescence examinations located KRT81 within the cytoplasm. Additionally, in KRT81-knockdown MDA-MB231 cells, zymography illustrated decreased MMP9 activity, while scratch and invasion assays demonstrated diminished cell migration and invasion capabilities. [9] This presents the first evidence of complete KRT81 expression in both normal breast epithelial cells and breast cancer cells. Furthermore, the findings suggest that KRT81 plays a role in the migration and invasion of breast cancer cells.

Related Research Articles

<span class="mw-page-title-main">Keratin</span> One of a family of fibrous structural proteins

Keratin is one of a family of structural fibrous proteins also known as scleroproteins. Alpha-keratin (α-keratin) is a type of keratin found in vertebrates. It is the key structural material making up scales, hair, nails, feathers, horns, claws, hooves, and the outer layer of skin among vertebrates. Keratin also protects epithelial cells from damage or stress. Keratin is extremely insoluble in water and organic solvents. Keratin monomers assemble into bundles to form intermediate filaments, which are tough and form strong unmineralized epidermal appendages found in reptiles, birds, amphibians, and mammals. Excessive keratinization participate in fortification of certain tissues such as in horns of cattle and rhinos, and armadillos' osteoderm. The only other biological matter known to approximate the toughness of keratinized tissue is chitin. Keratin comes in two types, the primitive, softer forms found in all vertebrates and harder, derived forms found only among sauropsids.

<span class="mw-page-title-main">Intermediate filament</span> Cytoskeletal structure

Intermediate filaments (IFs) are cytoskeletal structural components found in the cells of vertebrates, and many invertebrates. Homologues of the IF protein have been noted in an invertebrate, the cephalochordate Branchiostoma.

<span class="mw-page-title-main">Keratin 7</span>

Keratin, type II cytoskeletal 7 also known as cytokeratin-7 (CK-7) or keratin-7 (K7) or sarcolectin (SCL) is a protein that in humans is encoded by the KRT7 gene. Keratin 7 is a type II keratin. It is specifically expressed in the simple epithelia lining the cavities of the internal organs and in the gland ducts and blood vessels.

<span class="mw-page-title-main">Keratin 6A</span>

Keratin 6A is one of the 27 different type II keratins expressed in humans. Keratin 6A was the first type II keratin sequence determined. Analysis of the sequence of this keratin together with that of the first type I keratin led to the discovery of the four helical domains in the central rod of keratins. In humans Keratin 6A is encoded by the KRT6A gene.

Type II keratins constitutes the Type II intermediate filaments (IFs) of the intracytoplasmatic cytoskeleton, which is present in all mammalian epithelial cells. The type 2 cytokeratins consist of basic or neutral, high molecular weight proteins which in vivo are arranged in pairs of heterotypic Type I and Type II keratin chains, coexpressed during differentiation of simple and stratified epithelial tissues. It has been seen that Type II Keratins are developed before Type 1 keratins during human embryonic development.

<span class="mw-page-title-main">Keratin 14</span> Protein-coding gene in the species Homo sapiens

Keratin 14 is a member of the type I keratin family of intermediate filament proteins. Keratin 14 was the first type I keratin sequence determined. Keratin 14 is also known as cytokeratin-14 (CK-14) or keratin-14 (KRT14). In humans it is encoded by the KRT14 gene.

<span class="mw-page-title-main">Keratin 13</span> Protein-coding gene in the species Homo sapiens

Keratin 13 is a protein that in humans is encoded by the KRT13 gene.

<span class="mw-page-title-main">Keratin 19</span> Protein-coding gene in the species Homo sapiens

Keratin, type I cytoskeletal 19 also known as cytokeratin-19 (CK-19) or keratin-19 (K19) is a 40 kDa protein that in humans is encoded by the KRT19 gene. Keratin 19 is a type I keratin.

<span class="mw-page-title-main">Keratin 18</span>

Keratin 18 is a type I cytokeratin. It is, together with its filament partner keratin 8, perhaps the most commonly found products of the intermediate filament gene family. They are expressed in single layer epithelial tissues of the body. Mutations in this gene have been linked to cryptogenic cirrhosis. Two transcript variants encoding the same protein have been found for this gene.

<span class="mw-page-title-main">Keratin 16</span> Protein-coding gene in the species Homo sapiens

Keratin 16 is a protein that in humans is encoded by the KRT16 gene.

<span class="mw-page-title-main">Keratin 15</span> Protein-coding gene in the species Homo sapiens

Keratin 15 is a protein that in humans is encoded by the KRT15 gene. It has also been referred to as cytokeratin 15, K1CO and KRTB.

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

Cytokeratins are keratin proteins found in the intracytoplasmic cytoskeleton of epithelial tissue. They are an important component of intermediate filaments, which help cells resist mechanical stress. Expression of these cytokeratins within epithelial cells is largely specific to particular organs or tissues. Thus they are used clinically to identify the cell of origin of various human tumors.

<span class="mw-page-title-main">Keratin 8</span>

Keratin, type II cytoskeletal 8 also known as cytokeratin-8 (CK-8) or keratin-8 (K8) is a keratin protein that is encoded in humans by the KRT8 gene. It is often paired with keratin 18.

<span class="mw-page-title-main">Keratin 5</span>

Keratin 5, also known as KRT5, K5, or CK5, is a protein that is encoded in humans by the KRT5 gene. It dimerizes with keratin 14 and forms the intermediate filaments (IF) that make up the cytoskeleton of basal epithelial cells. This protein is involved in several diseases including epidermolysis bullosa simplex and breast and lung cancers.

<span class="mw-page-title-main">Keratin 6C</span>

Keratin 6C, is a type II cytokeratin, one of a number of isoforms of keratin 6 encoded by separate genes located within the type II keratin gene cluster on human chromosome 12q. This gene was uncovered recently by the Human Genome Project and its expression patterns in humans remains unknown.

<span class="mw-page-title-main">KRT81</span>

Keratin, type II cuticular Hb1 is a protein that in humans is encoded by the KRT81 gene.

<span class="mw-page-title-main">KRT23</span> Protein-coding gene in the species Homo sapiens

Keratin, type I cytoskeletal 23 is a protein that in humans is encoded by the KRT23 gene.

<span class="mw-page-title-main">KRT32</span> Protein-coding gene in the species Homo sapiens

Keratin, type I cuticular Ha2 is a protein that in humans is encoded by the KRT32 gene.

<span class="mw-page-title-main">Keratin 34</span> Protein-coding gene in the species Homo sapiens

Keratin, type I cuticular Ha4 is a protein that in humans is encoded by the KRT34 gene.

<span class="mw-page-title-main">KRT71</span> Protein-coding gene in humans

KRT71 is a keratin gene. Keratins are intermediate filament proteins responsible for the structural integrity of epithelial cells and are subdivided into epithelial keratins and hair keratins. This gene encodes a protein that is expressed in the inner root sheath of hair follicles. The type II keratins are clustered in a region of chromosome 12q13.

References

  1. 1 2 Rogers MA, Langbein L, Praetzel-Wunder S, Winter H, Schweizer J (January 2006). "Human hair keratin-associated proteins (KAPs)". International Review of Cytology. Academic Press. 251: 209–263. doi:10.1016/S0074-7696(06)51006-X. ISBN   9780123646552. PMID   16939781 . Retrieved 2023-11-28.
  2. 1 2 Cruz CF, Azoia NG, Matamá T, Cavaco-Paulo A (August 2017). "Peptide-protein interactions within human hair keratins". International Journal of Biological Macromolecules. 101: 805–814. doi:10.1016/j.ijbiomac.2017.03.052. hdl: 1822/56408 . PMID   28315768.
  3. ↑ Yu J, Yu DW, Checkla DM, Freedberg IM, Bertolino AP (July 1993). "Human hair keratins". The Journal of Investigative Dermatology. 101 (1 Suppl): 56S–59S. doi:10.1111/1523-1747.ep12362635. PMID   7686952.
  4. 1 2 Moll R, Divo M, Langbein L (June 2008). "The human keratins: biology and pathology". Histochemistry and Cell Biology. 129 (6): 705–733. doi:10.1007/s00418-008-0435-6. PMC   2386534 . PMID   18461349.
  5. 1 2 Gao F, Li W, Deng J, Kan J, Guo T, Wang B, Hao S (May 2019). "Recombinant Human Hair Keratin Nanoparticles Accelerate Dermal Wound Healing". ACS Applied Materials & Interfaces. 11 (20): 18681–18690. doi:10.1021/acsami.9b01725. PMID   31038908. S2CID   141367865.
  6. 1 2 Guo T, Li W, Wang J, Luo T, Lou D, Wang B, Hao S (2018). "Recombinant human hair keratin proteins for halting bleeding". Artificial Cells, Nanomedicine, and Biotechnology. 46 (sup2): 456–461. doi: 10.1080/21691401.2018.1459633 . PMID   29621887. S2CID   4620386.
  7. 1 2 Fujikawa H, Fujimoto A, Farooq M, Ito M, Shimomura Y (July 2012). "Characterization of the human hair keratin-associated protein 2 (KRTAP2) gene family". The Journal of Investigative Dermatology. 132 (7): 1806–1813. doi: 10.1038/jid.2012.73 . PMID   22495175.
  8. 1 2 3 Powell BC, Nesci A, Rogers GE (December 1991). "Regulation of keratin gene expression in hair follicle differentiation". Annals of the New York Academy of Sciences. 642: 1–20. doi:10.1111/j.1749-6632.1991.tb24376.x. PMID   1725577. S2CID   33504645.
  9. 1 2 3 4 Nanashima N, Horie K, Yamada T, Shimizu T, Tsuchida S (May 2017). "Hair keratin KRT81 is expressed in normal and breast cancer cells and contributes to their invasiveness". Oncology Reports. 37 (5): 2964–2970. doi: 10.3892/or.2017.5564 . PMID   28405679.
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