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Analysis of the expression pattern of involucrin in human scalp skin and hair follicles: hair cycle-associated alterations

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Abstract

Involucrin is a structural component of the keratinocyte cornified envelope that is expressed early in the keratinocyte differentiation process. It is a component of the initial envelope scaffolding and considered as a marker for keratinocyte terminal differentiation. The expression pattern of involucrin in human scalp skin and hair follicle cycle stages is not fully explored. This study addresses this issue and tests the hypothesis that “the expression of involucrin undergoes hair follicle cycle-dependent changes”. A total of 50 normal human scalp skin biopsies were examined (healthy females, 51–62 years) using immunofluorescence staining methods and real-time PCR analysis. In each case, 50 hair follicles were analyzed (35, 10 and 5 follicles in anagen, catagen and telogen, respectively). Involucrin was prominently expressed in the human scalp skin and hair follicles, on both gene and protein levels. The protein expression showed hair follicle cycle-associated changes i.e. a very strong expression during early and mature anagen, intermediate to strong expression during catagen and prominent decline in the telogen phase. The expression value of involucrin in both anagen and catagen was statistically significantly higher than that of telogen hair follicles (p < 0.001). This study provides the first morphologic indication that involucrin is differentially expressed in the human scalp skin and hair follicles and reports that involucrin expression pattern undergoes hair cycle-dependent changes. The clinical ramifications of these findings are open for further investigations.

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Abbreviations

ABC:

Avidin–bioltin complex

AWS:

Average weighted score

ClH:

Club hair

CTS:

Connective tissue sheath

DP:

Dermal papilla

HCo:

Hair cortex

HF:

Hair follicles

HMC:

Hair matrix cells

HMe:

Hair medulla

HS:

Hair shaft

INF:

Infundibulum

IR:

Immunoreactivity

IRS:

Inner root sheath

IR-score:

Immunoreactivity score

ISTH:

Isthmus

ORS:

Outer root sheath

SG:

Sebaceous gland

TSA:

Tyramide signal amplification

References

  • Adly MA, Assaf H, Nada EA, Soliman M, Hussein MR (2005) Human scalp skin and hair follicles express neurotrophin-3 and its high-affinity receptor tyrosine kinase C, and show hair cycle-dependent alterations in expression. Br J Dermatol 153(3):514–520

    Article  PubMed  CAS  Google Scholar 

  • Adly MA, Assaf H, Hussein MR (2006) Age-associated decrease of the nerve growth factor protein expression in the human skin: preliminary findings. J Dermatol Sci 42:268–271

    Article  PubMed  CAS  Google Scholar 

  • Adly MA, Assaf HA, Pertile P et al (2008a) Expression patterns of the glial cell line-derived neurotrophic factor, neurturin, their cognate receptors GFRalpha-1, GFRalpha-2, and a common signal transduction element c-Ret in the human skin hair follicles. J Am Acad Dermatol 58:238–250

    Article  PubMed  Google Scholar 

  • Adly MA, Assaf HA, Hussein MR (2008b) Heat shock protein 27 expression in the human testis showing normal and abnormal spermatogenesis. Cell Biol Int 32(10):1247–1255

    Article  PubMed  CAS  Google Scholar 

  • Adly MA, Assaf H, Hussein MR (2009) Expression pattern of p75 neurotrophin receptor protein in the human scalp skin and hair follicle: hair cycle-dependent expression. J Am Acad Dermatol 42:268–271

    Google Scholar 

  • Alibardi L (2011) Ultrastructural immunolocalization of involucrin in the medulla and inner root sheath of the human hair. Ann Anat. doi:10.1016/j.aanat.2011.10.012

  • Balasubramanian S, Efimova T, Eckert RL (2002) Green tea polyphenol stimulates a Ras, MEKK1, MEK3, and p38 cascade to increase activator protein 1 factor-dependent involucrin gene expression in normal human keratinocytes. J Biol Chem 277:1828–1836

    Article  PubMed  CAS  Google Scholar 

  • Banks-Schlegel S, Green H (1981) Involucrin synthesis and tissue assembly by keratinocytes in natural and cultural human epithelia. J Cell Biol 90:732–737

    Article  PubMed  CAS  Google Scholar 

  • Christophers E, Kligman AM (1965) Percutaneous absorption in aged skin. In: Montagna W (ed) Advances in the biology of skin, vol 6. Pergmamon, Oxford, p 163

    Google Scholar 

  • Crish JF, Howard JM, Zaim TM et al (1993) Tissue–specific and differentiation–appropriate expression of the human involucrin gene in transgenic mice: an abnormal epidermal phenotype. Differentiation 53:191

    Article  PubMed  CAS  Google Scholar 

  • Dawber RPR (1991) Hair follicle structure, keratinisation and the physical properties of hair. In: Rook A, Dawber RPR (eds) Disases of the hair and scalp, 2nd edn. Blackwell Scientific Publications, Oxford, pp 18–50

    Google Scholar 

  • de Viragh PA, Huber M, Hohl D (1994) Involucrin mRNA is more abundant in human hair follicles than in normal epidermis. J Invest Dermatol 103(6):815–819

    Article  PubMed  Google Scholar 

  • Dover R, Watt F (1987) Measurement of the rate of epidermal terminal differentiation: expression of involucrin by S-phase keratinocytes in culture and in psoriatic plaques. J Invest Dermatol 89:349–352

    Article  PubMed  CAS  Google Scholar 

  • Eckert RL (1989) Structure, function and differentiation of the keratinocyte. Physiol Rev 69:1316

    PubMed  CAS  Google Scholar 

  • Eckert RL, Green H (1986) Structure and evolution of the human involucrin gene. Cell 46:583–589

    Article  PubMed  CAS  Google Scholar 

  • Efimova T, Eckert RL (2000) Regulation of human involucrin promoter activity by novel protein kinase C isoforms. J Biol Chem 275:1601–1607

    Article  PubMed  CAS  Google Scholar 

  • Efimova T, LaCelle P, Welter JF, Eckert RL (1998) Regulation of human involucrin promoter activity by a protein kinase C, Ras, MEKK1, MEK3, p38/RK, AP1 signal transduction pathway. J Biol Chem 273:24387–24395

    Article  PubMed  CAS  Google Scholar 

  • Enikanolaive A, Lariviere N, Troy TC et al (2010) Involucrin-claudin-6 tail deletion mutant (CDelta206) transgenic mice: a model of delayed epidermal permeability barrier formation and repair. Dis Model Mech 3(3–4):167–180

    Article  Google Scholar 

  • Greco M, Lorand L, Lane W et al (1995) The pancornulins: a group of proline rich–related cornified envelope precursors with bifunctional capabilities in isopeptide bond formation. J Invest Dermatol 104:204–210

    Article  PubMed  CAS  Google Scholar 

  • Henry J, Toulza E, Hsu CY et al (2012) Update on the epidermal differentiation complex. Front Biosci 17:1517–1532

    Article  PubMed  CAS  Google Scholar 

  • Hohl D, Olano BR, de Viragh PA, Huber M, Detrisac CJ et al (1993) Expression pattern of loricrin in various species and tissues. Differentiation 54:25–34

    PubMed  CAS  Google Scholar 

  • Ishida-Yamamoto A, Lizuka H (1995) Differences in involucrin immunolabeling within cornified cell envelopes in normal and psoriatic epidermis. J Invest Dermatol 104:391–395

    Article  PubMed  CAS  Google Scholar 

  • Latham JA, Redfern CP, Thody AJ et al (1989) Immunohistochemical markers of human sebaceous gland differentiation. J Histochem Cytochem 37(5):729–734

    Article  PubMed  CAS  Google Scholar 

  • Müller-Rover S, Handijiski B, Van Der Veen C, Eichmuller S, Foitzik K, McKay I, Stenn KS, Paus R (2001) A comprehensive guide for the accurate classification of murine hair follicles in distinct hair cycle stages. J Invest Dermatol 117(1):3–15

    Article  PubMed  Google Scholar 

  • Murphy GF, Flynn TC, Rice RH, Pinkus G (1984) Involucrin expression in normal and neoplastic human skin: a marker for keratinocyte differentiation. J Invest Dermatol 84:453–457

    Article  Google Scholar 

  • Paus R (1998) Principles of hair cycle control. J Dermatol 25:793–802

    PubMed  CAS  Google Scholar 

  • Paus R, Cotsarelis G (1999) The biology of hair follicles. N Engl J Med 341:491–497

    Article  PubMed  CAS  Google Scholar 

  • Paus R, Muller-Rover S, Van Der Veen C, Maurer M, Eichmuller S, Ling G, Hofmann U, Foitzik K, Mecklenburg L, Handjiski B (1999) A comprehensive guide for the recognition and classification of distinct stages of hair follicle morphogenesis. J Invest Dermatol 113:523–532

    Article  PubMed  CAS  Google Scholar 

  • Pereda M, Dieamant G, Eberlin S, Werka R et al (2010) Expression of differential genes involved in the maintenance of water balance in human skin by Piptadenia colubrina extract. J Cos Dermatol 9(10):35–43

    Google Scholar 

  • Reichert J, Breiden B, Sandhoff K, Magin TM (2004) Loss of keratin 10 is accompanied by increased sebocyte proliferation and differentiation. Eur J Cell Biol 83:747–759

    Article  Google Scholar 

  • Rice RH, Green H (1979) Presence in human epidermal cells of a soluble protein precursor of the cross-linked envelope: activation of the cross-linking by calcium ions. Cell 18:681–694

    Article  PubMed  CAS  Google Scholar 

  • Robinson N, LaCelle P, Eckert R (1996) Involucrin is a covalently crosslinked constituent of highly purified epidermal corneocytes: evidence for a common pattern of involucrin crosslinking in vivo and in vitro. J Invet Dermatol 107:101–107

    Article  CAS  Google Scholar 

  • Rogers G, Koike K (2009) Laser capture microscopy in a study of expression of structural proteins in the cuticle cells of human hair. Exp Dermatol 18(6):541–547

    Article  PubMed  CAS  Google Scholar 

  • Roskos K, Maibach H, Guy R (1989) The effect of aging on percutaneous absorption in man. J Pharmacokinet Pharmacodynam 17(6):617–630

    Article  CAS  Google Scholar 

  • Said J, Sassoon A, Shintaku P, Banks-Schlegel S (1984) Involucrin in squamous and basal cell carcinomas of the skin: an immunohistochemical study. J Invest Dermatol 82:449–452

    Article  PubMed  CAS  Google Scholar 

  • Steinert PM, Marekov LN (1995) The proteins elafin, filaggrin, keratin intermediate filaments, loricin and small proline–rich proteins 1and 2 are isodipeptide cross-linked components of human epidermal cornified cell envelope. J Biol Chem 270:17702

    Article  PubMed  CAS  Google Scholar 

  • Steinert PM, Marekov LN (1997) Direct evidence that involucrin is a major early isopeptide crosslinked component of the keratinocyte cornified cell envelope. J Biol Chem 272:2021–2030

    Article  PubMed  CAS  Google Scholar 

  • Steinert PM, Parry DAD, Mareckov LN (2003) Trichohyalin mechanically strengthens the hair follicle. J Biol Chem 278:41409–41419

    Article  PubMed  CAS  Google Scholar 

  • Stenn KS, Paus R (2001) Controls of hair follicle cycling. Phys Rev 81(1):449–494

    CAS  Google Scholar 

  • Takahashi M, Tezuka T, Katunuma N (1992) Phosphorylated cystatin alpha is a natural substrate of epidermal transglutaminase for formation of skin cornified cell envelope. FEBS Lett 308:79–82

    Article  PubMed  CAS  Google Scholar 

  • Taresa E, Marekov LN, Andreoli J et al (1997) The fate of trichohyalin. J Biol Chem 272:27893–27901

    Article  Google Scholar 

  • Watt FM (1983) Involucrin and other markers of keratinocyte terminal differentiation. J Invest Dermatol 81:100–103

    Article  Google Scholar 

  • Yaffe MB, Beegen H, Eckert RL (1992) Biophysical characterization of involucrin reveals a molecule ideally suited to function as an intermolecular cross-bridge of the keratinocyte cornified envelope. J Biol Chem 276:12233–12238

    Google Scholar 

  • Yaffe MB, Murthy S, Eckert RL (1993) Evidence that involucrin is a covalently linked constituent of the highly purified cultured keratinocyte cornified envelopes. J Invest Dermatol 100:3–9

    Article  PubMed  CAS  Google Scholar 

  • Yoneda K, Steinert PM (1993) Overexpression of human loricrin in transgenic mice produces a normal phenotype. PNAS 90(22):10754–10758

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

The kind help of Dr. M. R. Hussein for his kind help in the confirmation of the semiquantitative data is greatly acknowledged. This work was supported by Sohag University, Egypt.

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Correspondence to Mohamed A. Adly.

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Adly, M.A., Assaf, H.A. Analysis of the expression pattern of involucrin in human scalp skin and hair follicles: hair cycle-associated alterations. Histochem Cell Biol 138, 683–692 (2012). https://doi.org/10.1007/s00418-012-0986-4

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