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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. 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.
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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). 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.
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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. 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.
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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. 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.
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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. 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.
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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. 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.
71:, 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 . 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.
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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.
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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
341:
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). Reverse transcription-polymerase chain reaction confirmed the expression
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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
79:
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
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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. Keratins belong to two
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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. The
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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.
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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
54:
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
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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
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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. However, this intricate process can be simplified into a few highly preserved gene families. In cortical
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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.
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breast epithelial cells. Moreover, the expressed KRT81 was found to be a 5′-truncated isoform (ΔHb1), with the full-length protein not being expressed. However, the exact function of this truncated form in breast cancer cells remains unclear.
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evolves into one of the most complex structures in the human body, comprising 7–8 distinct tissue sections. The base of the hair follicle contains the bulb, housing dermal fibroblasts known as the
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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
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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".
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to create a heterodimer, which then aggregates into higher-order structural units. Similar to other intermediate filament
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Powell BC, Nesci A, Rogers GE (December 1991). "Regulation of keratin gene expression in hair follicle differentiation".
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Cruz CF, Azoia NG, Matamá T, Cavaco-Paulo A (August 2017). "Peptide-protein interactions within human hair keratins".
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750:"Hair keratin KRT81 is expressed in normal and breast cancer cells and contributes to their invasiveness"
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Yu J, Yu DW, Checkla DM, Freedberg IM, Bertolino AP (July 1993). "Human hair keratins".
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654:"Characterization of the human hair keratin-associated protein 2 (KRTAP2) gene family"
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Rogers MA, Langbein L, Praetzel-Wunder S, Winter H, Schweizer J (January 2006).
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Nanashima N, Horie K, Yamada T, Shimizu T, Tsuchida S (May 2017).
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Fujikawa H, Fujimoto A, Farooq M, Ito M, Shimomura Y (July 2012).
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Guo T, Li W, Wang J, Luo T, Lou D, Wang B, Hao S (2018).
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16:Type of keratin found in hair and nails
556:ACS Applied Materials & Interfaces
106:There are two types of hair keratin:
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1488:Cartilage oligomeric matrix protein
55:associated proteins known as KAPs.
712:10.1111/j.1749-6632.1991.tb24376.x
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367:International Review of Cytology
508:Histochemistry and Cell Biology
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619:10.1080/21691401.2018.1459633
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1252:Cartilage associated protein
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373:. Academic Press: 209–263.
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796:Medical Subject Headings
792:Keratins,+Hair-Specific
568:10.1021/acsami.9b01725
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283:type II hair keratin 6
272:type II hair keratin 5
261:type II hair keratin 4
250:type II hair keratin 3
239:type II hair keratin 2
228:type II hair keratin 1
152:type I hair keratin 3B
141:type I hair keratin 3A
1266:Procollagen peptidase
324:Clinical significance
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207:type I hair keratin 8
196:type I hair keratin 7
185:type I hair keratin 6
174:type I hair keratin 5
163:type I hair keratin 4
130:type I hair keratin 2
119:type I hair keratin 1
58:Keratin is a crucial
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472:(1 Suppl): 56S–59S.
223:type II hair keratin
671:10.1038/jid.2012.73
562:(20): 18681–18690.
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114:type I hair keratin
1432:Matrix gla protein
1243:Prolyl hydroxylase
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242:
231:
222:
210:
199:
188:
177:
166:
155:
144:
133:
122:
113:
105:
96:
87:
78:
65:polypeptides
57:
41:
20:Hair keratin
19:
18:
1473:Cytokeratin
1402:Vitronectin
1083:multiplexin
427:: 805–814.
1104:Endostatin
1093:type XVIII
442:1822/56408
402:2023-11-28
346:References
1483:Reticulin
1176:type VIII
584:141367865
75:Stability
26:found in
1519:Keratins
1513:Category
1498:diseases
1494:See also
1437:Tectorin
1256:Leprecan
1166:type VII
996:type XII
919:type III
872:Collagen
809:30 March
776:28405679
728:33504645
706:: 1–20.
680:22495175
628:29621887
576:31038908
538:18461349
451:28315768
397:16939781
38:Function
30:and the
1478:Gelatin
1469:Keratin
1417:Decorin
1390:Elastin
1285:Laminin
1261:ADAMTS2
1235:Enzymes
1225:COL28A1
1220:COL27A1
1213:COL11A2
1208:COL11A1
1203:type XI
1197:COL10A1
1138:type VI
1135:other:
1129:COL25A1
1124:COL23A1
1119:COL17A1
1114:COL13A1
1099:COL18A1
1087:COL15A1
1043:type IV
1031:COL22A1
1026:COL21A1
1021:COL20A1
1016:COL19A1
1011:COL16A1
1006:COL14A1
1000:COL12A1
974:type IX
954:COL26A1
949:COL24A1
907:type II
849:Protein
720:1725577
636:4620386
529:2386534
486:7686952
24:keratin
1422:FAM20C
1193:type X
1186:COL8A2
1181:COL8A1
1170:COL7A1
1159:COL6A5
1154:COL6A3
1149:COL6A2
1144:COL6A1
1074:COL4A6
1069:COL4A5
1064:COL4A4
1059:COL4A3
1054:COL4A2
1049:COL4A1
989:COL9A3
984:COL9A2
979:COL9A1
942:COL5A3
937:COL5A2
932:COL5A1
926:type V
912:COL2A1
899:COL1A2
894:COL1A1
888:type I
863:matrix
798:(MeSH)
774:
726:
718:
678:
634:
626:
582:
574:
536:
526:
484:
449:
395:
385:
157:KRT33B
146:KRT33A
111:acidic
1462:Other
1447:TECTB
1442:TECTA
1412:FREM2
1407:FRAS1
1385:ALCAM
1378:Other
1367:LAMC3
1362:LAMC2
1357:LAMC1
1352:gamma
1345:LAMB4
1340:LAMB3
1335:LAMB2
1330:LAMB1
1318:LAMA5
1313:LAMA4
1308:LAMA3
1303:LAMA2
1298:LAMA1
1293:alpha
970:FACIT
963:Other
724:S2CID
632:S2CID
580:S2CID
288:KRT86
277:KRT85
266:KRT84
255:KRT83
244:KRT82
233:KRT81
220:basic
212:KRT38
201:KRT37
190:KRT36
179:KRT35
168:KRT34
135:KRT32
124:KRT31
102:Types
32:nails
1427:ECM1
1325:beta
811:2017
772:PMID
716:PMID
676:PMID
624:PMID
572:PMID
534:PMID
482:PMID
447:PMID
393:PMID
383:ISBN
28:hair
762:doi
708:doi
704:642
666:doi
662:132
614:doi
564:doi
524:PMC
516:doi
512:129
474:doi
470:101
437:hdl
429:doi
425:101
375:doi
371:251
1515::
1085::
1040::
972::
851::
770:.
758:37
756:.
752:.
736:^
722:.
714:.
702:.
688:^
674:.
660:.
656:.
644:^
630:.
622:.
610:46
608:.
604:.
592:^
578:.
570:.
560:11
558:.
546:^
532:.
522:.
510:.
506:.
494:^
480:.
468:.
445:.
435:.
423:.
411:^
391:.
381:.
369:.
365:.
353:^
285:,
274:,
263:,
252:,
241:,
230:,
209:,
198:,
187:,
176:,
165:,
154:,
143:,
132:,
121:,
34:.
1471:/
1254:/
1245:/
1199:)
1195:(
1172:)
1168:(
1002:)
998:(
914:)
910:(
841:e
834:t
827:v
813:.
778:.
764::
730:.
710::
682:.
668::
638:.
616::
586:.
566::
540:.
518::
488:.
476::
453:.
439::
431::
405:.
377::
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