Loss of Keratin 6 (K6) Proteins Reveals a Function for Intermediate Filaments During Wound Repair

Overview

Journal J Cell Biol

Specialty Cell Biology

Date 2003 Oct 22

PMID 14568992

Citations 83

Authors

Pauline Wong

Pierre A Coulombe

Affiliations

Soon will be listed here.

Abstract

The ability to heal wounds is vital to all organisms. In mammalian tissues, alterations in intermediate filament (IF) gene expression represent an early reaction of cells surviving injury. We investigated the role of keratin IFs during the epithelialization of skin wounds using a keratin 6alpha and 6beta (K6alpha/K6beta)-null mouse model. In skin explant culture, null keratinocytes exhibit an enhanced epithelialization potential due to increased migration. The extent of the phenotype is strain dependent, and is accompanied by alterations in keratin IF and F-actin organization. However, in wounded skin in vivo, null keratinocytes rupture as they attempt to migrate under the blood clot. Fragility of the K6alpha/K6beta-null epidermis is confirmed when applying trauma to chemically treated skin. We propose that the alterations in IF gene expression after tissue injury foster a compromise between the need to display the cellular pliability necessary for timely migration and the requirement for resilience sufficient to withstand the rigors of a wound site.

Citing Articles

Understanding the early molecular changes associated with radiation therapy-A preliminary bulk RNA sequencing study.

Miller A, De May H, Rou D, Agarwal J, Jeyapalina S PLoS One. 2025; 20(3):e0316443.

PMID: 40029831 PMC: 11875373. DOI: 10.1371/journal.pone.0316443.

eIF6 modulates skin wound healing by upregulating keratin 6B.

Wang X, Xu G, Zhang F, Wei Y, Deng J, Mu L Stem Cells Transl Med. 2024; 13(11):1101-1112.

PMID: 39406496 PMC: 11555475. DOI: 10.1093/stcltm/szae064.

Keratins 6, 16, and 17 in Health and Disease: A Summary of Recent Findings.

Romashin D, Tolstova T, Varshaver A, Kozhin P, Rusanov A, Luzgina N Curr Issues Mol Biol. 2024; 46(8):8627-8641.

PMID: 39194725 PMC: 11352355. DOI: 10.3390/cimb46080508.

Postbiotic lactobacilli induce cutaneous antimicrobial response and restore the barrier to inhibit the intracellular invasion of Staphylococcus aureus in vitro and ex vivo.

Dinic M, Burgess J, Lukic J, Catanuto P, Radojevic D, Marjanovic J FASEB J. 2024; 38(14):e23801.

PMID: 39018106 PMC: 11258854. DOI: 10.1096/fj.202400054RR.

Shifts in keratin isoform expression activate motility signals during wound healing.

Nanes B, Bhatt K, Azarova E, Rajendran D, Munawar S, Isogai T Dev Cell. 2024; 59(20):2759-2771.e11.

PMID: 39002537 PMC: 11496015. DOI: 10.1016/j.devcel.2024.06.011.

References

Lepekhin E, Eliasson C, Berthold C, Berezin V, Bock E, Pekny M . Intermediate filaments regulate astrocyte motility. J Neurochem. 2001; 79(3):617-25. DOI: 10.1046/j.1471-4159.2001.00595.x. View

Bousquet O, Ma L, Yamada S, Gu C, Idei T, Takahashi K . The nonhelical tail domain of keratin 14 promotes filament bundling and enhances the mechanical properties of keratin intermediate filaments in vitro. J Cell Biol. 2001; 155(5):747-54. PMC: 2150872. DOI: 10.1083/jcb.200104063. View

Tanaka H, Katoh A, Oguro K, Shimazaki K, Gomi H, Itohara S . Disturbance of hippocampal long-term potentiation after transient ischemia in GFAP deficient mice. J Neurosci Res. 2001; 67(1):11-20. DOI: 10.1002/jnr.10004. View

Coulombe P, Omary M . 'Hard' and 'soft' principles defining the structure, function and regulation of keratin intermediate filaments. Curr Opin Cell Biol. 2002; 14(1):110-22. DOI: 10.1016/s0955-0674(01)00301-5. View

McGowan K, Coulombe P . The wound repair-associated keratins 6, 16, and 17. Insights into the role of intermediate filaments in specifying keratinocyte cytoarchitecture. Subcell Biochem. 1999; 31:173-204. View

Pekny M, Johansson C, Eliasson C, Stakeberg J, Wallen A, Perlmann T . Abnormal reaction to central nervous system injury in mice lacking glial fibrillary acidic protein and vimentin. J Cell Biol. 1999; 145(3):503-14. PMC: 2185074. DOI: 10.1083/jcb.145.3.503. View

Irvine A, McLean W . Human keratin diseases: the increasing spectrum of disease and subtlety of the phenotype-genotype correlation. Br J Dermatol. 1999; 140(5):815-28. DOI: 10.1046/j.1365-2133.1999.02810.x. View

Moll R, Franke W, Schiller D, Geiger B, Krepler R . The catalog of human cytokeratins: patterns of expression in normal epithelia, tumors and cultured cells. Cell. 1982; 31(1):11-24. DOI: 10.1016/0092-8674(82)90400-7. View

Wong P, Takahashi K, Gu C, Babinet C, Coulombe P . Introducing a null mutation in the mouse K6alpha and K6beta genes reveals their essential structural role in the oral mucosa. J Cell Biol. 2000; 150(4):921-8. PMC: 2175283. DOI: 10.1083/jcb.150.4.921. View

10.

Coulombe P, Bousquet O, Ma L, Yamada S, Wirtz D . The 'ins' and 'outs' of intermediate filament organization. Trends Cell Biol. 2000; 10(10):420-8. DOI: 10.1016/s0962-8924(00)01828-6. View

11.

Toivola D, Baribault H, Magin T, Michie S, Omary M . Simple epithelial keratins are dispensable for cytoprotection in two pancreatitis models. Am J Physiol Gastrointest Liver Physiol. 2000; 279(6):G1343-54. DOI: 10.1152/ajpgi.2000.279.6.G1343. View

12.

Stenn K, Paus R . Controls of hair follicle cycling. Physiol Rev. 2001; 81(1):449-494. DOI: 10.1152/physrev.2001.81.1.449. View

13.

Smythe G, Davies M, Paulin D, Grounds M . Absence of desmin slightly prolongs myoblast proliferation and delays fusion in vivo in regenerating grafts of skeletal muscle. Cell Tissue Res. 2001; 304(2):287-94. DOI: 10.1007/s004410100366. View

14.

Vaittinen S, Lukka R, Sahlgren C, Hurme T, Rantanen J, Lendahl U . The expression of intermediate filament protein nestin as related to vimentin and desmin in regenerating skeletal muscle. J Neuropathol Exp Neurol. 2001; 60(6):588-97. DOI: 10.1093/jnen/60.6.588. View

15.

Wojcik S, Longley M, Roop D . Discovery of a novel murine keratin 6 (K6) isoform explains the absence of hair and nail defects in mice deficient for K6a and K6b. J Cell Biol. 2001; 154(3):619-30. PMC: 2196416. DOI: 10.1083/jcb.200102079. View

16.

Gilbert S, Loranger A, Daigle N, Marceau N . Simple epithelium keratins 8 and 18 provide resistance to Fas-mediated apoptosis. The protection occurs through a receptor-targeting modulation. J Cell Biol. 2001; 154(4):763-73. PMC: 2196458. DOI: 10.1083/jcb.200102130. View

17.

Anastasiadis P, Reynolds A . Regulation of Rho GTPases by p120-catenin. Curr Opin Cell Biol. 2001; 13(5):604-10. DOI: 10.1016/s0955-0674(00)00258-1. View

18.

Hesse M, Magin T, Weber K . Genes for intermediate filament proteins and the draft sequence of the human genome: novel keratin genes and a surprisingly high number of pseudogenes related to keratin genes 8 and 18. J Cell Sci. 2001; 114(Pt 14):2569-75. DOI: 10.1242/jcs.114.14.2569. View

19.

Wawersik M, Mazzalupo S, Nguyen D, Coulombe P . Increased levels of keratin 16 alter epithelialization potential of mouse skin keratinocytes in vivo and ex vivo. Mol Biol Cell. 2001; 12(11):3439-50. PMC: 60266. DOI: 10.1091/mbc.12.11.3439. View

20.

Tyner A, Fuchs E . Evidence for posttranscriptional regulation of the keratins expressed during hyperproliferation and malignant transformation in human epidermis. J Cell Biol. 1986; 103(5):1945-55. PMC: 2114388. DOI: 10.1083/jcb.103.5.1945. View