Top

Published in:

01-01-2019 | Original Paper

Podoplanin suppresses the cell adhesion of epidermal keratinocytes via functional regulation of β1-integrin

Authors: Takashi Shibuya, Masaru Honma, Mizue Fujii, Shin Iinuma, Akemi Ishida-Yamamoto

Published in: Archives of Dermatological Research | Issue 1/2019

Abstract

Epidermal stem cells adhere more efficiently to the extracellular matrix (ECM) than the less adhesive differentiating cells due to their high expression of cell adhesion molecules including β1-integrin. Podoplanin is majorly expressed in the markedly proliferative and differentiating basal cells of the wounded and psoriatic epidermis. This study was designed to reveal podoplanin’s function in human epidermal keratinocytes (HEK) focusing on its interaction with β1-integrin. We analyzed the adhesion and differentiation of HEK in both podoplanin-overexpressing and -knock-down cells, considering their β1-integrin levels. The basal layer of IL-22-treated hyperproliferative reconstituted epidermis cells (simulating basal hyperproliferative psoriatic epidermal basal cells) expressed higher podoplanin levels than the untreated control cells. The adhesiveness of HaCaT cells, which do not express podoplanin, was reduced after the overexpression of podoplanin. HEK with podoplanin overexpression suppressed the cell adhesion to type I collagen (while downregulating β1-integrin functions) and podoplanin silencing augmented it (by increasing active ECM-bound β1-integrin). The increased cell adhesion to type I collagen induced by podoplanin silencing could be reversed by addition of P5D2, a neutralizing antibody against β1-integrin. In the psoriatic epidermis, podoplanin expression was especially upregulated on the rete ridges of the basal cell layer. This expression pattern was inversely correlated with the total/ECM-bound active β1-integrin-expression, which was stronger at the basal cell layer covering the dermal papillae. Our results indicate that podoplanin inhibits the cell ECM attachment by suppressing β1-integrin and initiating HEK differentiation. Podoplanin is presumably involved in the pathogenesis of psoriasis.

Allen TD, Potten CS (1974) Fine-structural identification and organization of the epidermal proliferative unit. J Cell Sci 15:291–319PubMed

Billick E, Mitsui H, Gulati N, Fujita H, Gilleaudeau P, Sullivan-Whalen M, Johnson-Huang LM, Suárez-Fariñas M, Krueger JG (2012) Human keratinocytes’ response to injury upregulates CCL20 and other genes linking innate and adaptive immunity. J Investig Dermatol 132:105–113. https://doi.org/10.1038/jid.2011.262 CrossRefPubMed

Boehncke W-H, Schön MP (2015) Psoriasis. Lancet 386:983–994. https://doi.org/10.1016/S0140-6736(14)61909-7 CrossRefPubMed

Charruyer A, Fong S, Vitcov G, Sklar S, Tabernik L, Taneja M, Caputo M, Soeung C, Yue L, Uchida Y, Arron S, Horton K, Foster R, Sano S, North J, Ghadially R (2017) Brief report: interleukin-17A-dependent asymmetric stem cell divisions are increased in human psoriasis: a mechanism underlying benign hyperproliferation. Stem Cells 35:2001–2007CrossRefPubMed

Cueni LN, Detmar M (2009) Galectin-8 interacts with podoplanin and modulates lymphatic endothelial cell functions. Exp Cell Res 315:1715–1723. https://doi.org/10.1016/j.yexcr.2009.02.021 CrossRefPubMedPubMedCentral

Fuchs E, Raghavan S (2002) Getting under the skin of epidermal morphogenesis. Nat Rev Genet 3:199–209. https://doi.org/10.1038/nrg758 CrossRefPubMed

Fujii M, Honma M, Takahashi H, Ishida-Yamamoto A, Iizuka H (2012) Intercellular contact augments epidermal growth factor receptor (EGFR) and signal transducer and activator of transcription 3 (STAT3)-activation which increases podoplanin-expression in order to promote squamous cell carcinoma motility. Cell Signal 25:760–765. https://doi.org/10.1016/j.cellsig.2012.12.004 CrossRefPubMed

Haslett PA, Phipps KM, Krueger JG, Fretzin S, Cameron GS, Mccolm J, Katcherian A, Cueto I, White T (2012) IL-17A is essential for cell activation and inflammatory gene circuits in subjects with psoriasis. J Allergy Clin Immunol 130:145–154. https://doi.org/10.1016/j.jaci.2012.04.024 CrossRefPubMedPubMedCentral

Honma M, Benitah SA, Watt FM (2006) Role of LIM kinases in normal and psoriatic human epidermis. Mol Biol Cell 17:1888–1896CrossRefPubMedPubMedCentral

10.

Honma M, Fujii M, Iinuma S, Minami-Hori M, Takahashi H, Ishida-Yamamoto A, Iizuka H (2013) Podoplanin expression is inversely correlated with granular layer/filaggrin formation in psoriatic epidermis. J Dermatol 40:296–297. https://doi.org/10.1111/1346-8138.12060 CrossRefPubMed

11.

Honma M, Minami-Hori M, Takahashi H, Iizuka H (2012) Podoplanin expression in wound and hyperproliferative psoriatic epidermis: regulation by TGF-β and STAT-3 activating cytokines, IFN-γ, IL-6, and IL-22. J Dermatol Sci 65:134–140. https://doi.org/10.1016/j.jdermsci.2011.11.011 CrossRefPubMed

12.

Iizuka H, Ishida-Yamamoto A, Honda H (1996) Epidermal remodelling in psoriasis. Br J Dermatol 135:433–438CrossRefPubMed

13.

Jones PH, Simons BD, Watt FM (2007) Sic transit gloria: farewell to the epidermal transit amplifying cell? Cell Stem Cell 1:371–381. https://doi.org/10.1016/j.stem.2007.09.014 CrossRefPubMed

14.

Jones PH, Watt FM (1993) Separation of human epidermal stem cells from transit amplifying cells on the basis of differences in integrin function and expression. Cell 73:713–724CrossRefPubMed

15.

Kinouchi M, Takahashi H, Itoh Y, Ishida-Yamamoto A, Iizuka H (2002) Ultraviolet B irradiation increases keratin 5 and keratin 14 expression through epidermal growth factor receptor of SV40-transformed human keratinocytes. Arch Dermatol Res 293:634–641. https://doi.org/10.1007/s00403-001-0284-9 CrossRefPubMed

16.

Lowes MA, Bowcock AM, Krueger JG (2007) Pathogenesis and therapy of psoriasis. Nature 445:866–873. https://doi.org/10.1038/nature05663 CrossRefPubMed

17.

Mansbridge JN, Knapp AM (1987) Changes in keratinocyte maturation during wound healing. J Investig Dermatol 89:253–263CrossRefPubMed

18.

Margadant C, Frijns E, Wilhelmsen K, Sonnenberg A (2008) Regulation of hemidesmosome disassembly by growth factor receptors. Curr Opin Cell Biol 20:589–596. https://doi.org/10.1016/j.ceb.2008.05.001 CrossRefPubMed

19.

Martín-Villar E, Ferna B, Parsons M, Yurrita MM, Megías D, Pe E, Jones GE, Quintanilla M (2010) Podoplanin associates with CD44 to promote directional cell migration. Mol Biol Cell 21:4387–4399. https://doi.org/10.1091/mbc.E10 CrossRefPubMedPubMedCentral

20.

Namikawa K, Honma M, Abe K, Takeda M, Mansur K, Obata T, Miwa A, Okado H, Kiyama H (2000) Akt/protein kinase B prevents injury-induced motoneuron death and accelerates axonal regeneration. J Neurosci 20:2875–2886CrossRefPubMed

21.

Namkung JH, Kim E, Park YD, Park G, Yang JM (2015) Are podoplanin gene polymorphisms associated with atopic dermatitis in koreans? Ann Dermatol 27:275–282. https://doi.org/10.5021/ad.2015.27.3.275 CrossRefPubMedPubMedCentral

22.

Nestle FO, Kaplan DH, Barker J (2009) Psoriasis. N Engl J Med 361:496–509. https://doi.org/10.1056/NEJMra0804595 CrossRef

23.

Noack M, Ndongo-Thiam ND, Miossec P (2016) Role of podoplanin in the high interleukin-17A secretion resulting from interactions between activated lymphocytes and psoriatic skin-derived mesenchymal cells. Clin Exp Immunol 186:64–74. https://doi.org/10.1111/cei.12830 CrossRefPubMedPubMedCentral

24.

Ochoa-Alvarez JA, Krishnan H, Shen Y, Acharya NK, Han M, McNulty DE, Hasegawa H, Hyodo T, Senga T, Geng J-G, Kosciuk M, Shin SS, Goydos JS, Temiakov D, Nagele RG, Goldberg GS (2012) Plant lectin can target receptors containing sialic acid, exemplified by podoplanin, to inhibit transformed cell growth and migration. PLoS One 7:e41845. https://doi.org/10.1371/journal.pone.0041845 CrossRefPubMedPubMedCentral

25.

Papp KA, Reich K, Paul C, Blauvelt A, Baran W, Bolduc C, Toth D, Langley RG, Cather J, Gottlieb AB, Thac D (2016) A prospective phase III, randomized, double-blind, placebo-controlled study of brodalumab in patients with moderate-to-severe plaque psoriasis. Br J Dermatol 175:273–286. https://doi.org/10.1111/bjd.14493 CrossRefPubMed

26.

Peñas P (1998) Differential expression of activation epitopes of beta1 integrins in psoriasis and normal skin. J Investig Dermatol 111:19–24CrossRefPubMed

27.

Peñas PF, Gómez M, Buezo GF, Rios L, Yáñez-Mo M, Cabañas C, Sánchez-Madrid F, García-Díez A (1998) Differential expression of activation epitopes of β1 integrins in psoriasis and normal skin. J Investig Dermatol 111:19–24CrossRefPubMed

28.

Reichrath J, Horf R, Chen TC, Müller SM, Sanan D, Holick MF (1997) Expression of integrin subunits and CD44 isoforms in psoriatic skin and effects of topical calcitriol application. J Cutan Pathol 24:499–506CrossRefPubMed

29.

Schacht V, Ramirez MI, Hong YK, Hirakawa S, Feng D, Harvey N, Williams M, Dvorak AM, Dvorak HF, Oliver G, Detmar M (2003) T1alpha/podoplanin deficiency disrupts normal lymphatic vasculature formation and causes lymphedema. EMBO J 22:3546–3556. https://doi.org/10.1093/emboj/cdg342 CrossRefPubMedPubMedCentral

30.

Tsuneki M, Yamazaki M, Maruyama S, Cheng J, Saku T (2013) Podoplanin-mediated cell adhesion through extracellular matrix in oral squamous cell carcinoma. Lab Investig 93:921–932. https://doi.org/10.1038/labinvest.2013.86 CrossRefPubMed

31.

Watt FM (2002) Role of integrins in regulating epidermal adhesion, growth and differentiation. EMBO J 21:3919–3926CrossRefPubMedPubMedCentral

32.

Watt FM, Fujiwara H (2011) Cell-extracellular matrix interactions in normal and diseased skin. Cold Spring Harb Perspect Biol 3:a005124CrossRefPubMedPubMedCentral

33.

Weinstein G, Scott E van (1965) Autoradiographic analysis of turnover times of normal and psoriatic epidermis. J Investig Dermatol 45:257–263CrossRefPubMed

Title: Podoplanin suppresses the cell adhesion of epidermal keratinocytes via functional regulation of β1-integrin
Authors: Takashi Shibuya
Masaru Honma
Mizue Fujii
Shin Iinuma
Akemi Ishida-Yamamoto
Publication date: 01-01-2019
Publisher: Springer Berlin Heidelberg
Published in: Archives of Dermatological Research / Issue 1/2019
Print ISSN: 0340-3696
Electronic ISSN: 1432-069X
DOI: https://doi.org/10.1007/s00403-018-1878-9

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Podoplanin suppresses the cell adhesion of epidermal keratinocytes via functional regulation of β1-integrin

Abstract

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 1/2019

Mortality and risk factors among Israeli bullous pemphigoid patients

A randomized placebo-controlled single-center pilot study of the safety and efficacy of apremilast in subjects with moderate-to-severe alopecia areata

Leakage of sweat into the dermo-epidermal junction as a possible trigger for lichen planus lesion development

Small intestinal bacterial overgrowth in systemic sclerosis: a review of the literature

CXCL12 regulates differentiation of human immature melanocyte precursors as well as their migration

Evidence of proliferative activity in human Merkel cells: implications in the histogenesis of Merkel cell carcinoma