Top

Published in:

01-06-2003 | Original Paper

1,25-Dihydroxyvitamin D₃ increases human cystatin A expression by inhibiting the Raf-1/MEK1/ERK signaling pathway of keratinocytes

Authors: Hidetoshi Takahashi, Masaki Ibe, Masaru Honma, Akemi Ishida-Yamamoto, Yoshio Hashimoto, Hajime Iizuka

Published in: Archives of Dermatological Research | Issue 2/2003

Abstract

The active form of vitamin D₃, 1,25-dihydroxyvitamin D₃ (1,25(OH)₂D3), regulates proliferation and differentiation of keratinocytes. Cystatin A, a cysteine proteinase inhibitor, is a cornified cell envelope constituent and a differentiation marker of keratinocytes. In the present study, we examined the effect of 1,25(OH)₂D3 on the expression of cystatin A of cultured normal human keratinocytes (NHK). 1,25(OH)₂D3 suppressed NHK proliferation in a dose-dependent manner with the maximal effect at 1×10⁻⁷ M. It also stimulated cystatin A promoter activity and its expression with similar dose effects. The increased cystatin A was detected by 24 h and the effect was accompanied by the suppression of ERK activity. Cystatin A promoter activity was not affected by cotransfection of vitamin D₃ receptor or retinoid X receptor. Further analyses disclosed that the 12-o-tetradecanoylphorbol-13-acetate (TPA)-responsive element (TRE), T2 (−272 to −278), in cystatin A promoter is critical for the regulation by 1,25(OH)₂D3. Transfection of the dominant-negative form of ERK adenovirus (Ad-dnERK) increased cystatin A promoter activity and its expression, which was markedly augmented by 1,25(OH)₂D3 treatment. Transfection of the dominant-active form of Raf-1 (Ad-daRaf-1) or MEK1 (Ad-daMEK1) inhibited 1,25(OH)₂D3-dependent cystatin A promoter activity and its expression. Consistent with these results, the MEK1 inhibitor, PD98059, further augmented 1,25(OH)₂D3-induced cystatin A promoter activity and its expression. The present study demonstrated that the 1,25(OH)₂D3-responsive element in the cystatin A gene is identical to the TRE, T2 (−272 to −278), and that the suppression of Raf-1/MEK1/ERK1,2 signaling pathway increases cystatin A expression of NHK.

Walters MR (1992) Newly identified actions of the vitamin D system. Endocr Rev 13:719–764PubMed

Hosomi J, Hosoi J, Abe E, Suda T, Kuroki T (1983) Regulation of terminal differentiation of cultured mouse epidermal cells by 1α, 25-dihydroxyvitamin D₃. Endocrinology 113:1950–1957PubMed

Smith EL, Walworth NC, Holick MF (1986) Effect of 1α, 25-dihydroxyvitamin D₃ on the morphologic and biochemical differentiation of cultured human epidermal keratinocyte growth in serum-free condition. J Invest Dermatol 86:709–714PubMed

Pillai S, Bikle DD (1991) Role of intercellular-free calcium in the cornified envelope formation of keratinocytes: difference in the mode of the action of extracellular calcium and 1α, 25-dihydroxyvitamin D₃. J Cell Physiol 146:94–100PubMed

Umesono K, Murakami K, Thompson CC, Evans RM (1991) Direct repeat as selective response elements for the thyroid hormone, retinoic acid, and vitamin D₃ receptor. Cell 65:1255–1266PubMed

Carlberg C, Bendik I, Wyss E, Sturzenbecker LJ, Grippo JF, Hunziker W (1993) Two nuclear signaling pathways for vitamin D. Nature 361:657–660PubMed

Schrader M, Muller KM, Nayeri S, Kahlen JP, Carberg C (1994) Vitamin D₃-thyroid hormone receptor heterodimer polarity directs ligand sensitivity of transactivation. Nature 370:382–386PubMed

Marcinkowska E, Wiedlocha A, Radzikowski C (1997) 1α, 25-Dihydroxyvitamin D₃ induced activation and subsequent nuclear translocation of MAPK is upstream regulated by PKC in HL-60 cells. Biochem Biophys Res Commun 241:419–426CrossRefPubMed

Berry D, Antochi R, Bhatia M, Mecklinf-Gill KA (1996) 1α, 25-Dihydroxyvitamin D₃ stimulates expression and translocation of protein kinase Cα and Cδ via a non-genomic mechanism and rapidly induces phosphorylation of a 33-kDa protein an acute promyelocytic NB4 cells. J Biol Chem 271:16090–16096CrossRefPubMed

10.

Takahashi H, Tamura T, Iizuka H (1996) 1α, 25-Dihydroxyvitamin D₃ increased β-adrenergic adenylate cyclase response of fetal rat keratinizing epidermal cells (FRSK cells). J Dermatol Sci 11:121–128CrossRefPubMed

11.

de Boland AR, Norman AW (1990) Influx of extracellular calcium mediates 1α, 25-dihydroxyvitamin D₃-dependent transcaltachia (the rapid stimulation of duodenal Ca²⁺ transport). Endocrinology 127:2475–2480PubMed

12.

Norman AW, Nemere I, Bishop JE, Lowe KE, Maiyar AC, Collins ED, Taoka T, Sergreev I, Farach-Carson MC (1992) 1,25(OH)₂-Vitamin D₃, steroid hormone that produces biologic effects via both genomic and non-genomic pathway. J Steroid Biochem Mol Biol 41:231–240CrossRefPubMed

13.

Takahashi H, Kinouchi M, Wuepper KD, Iizuka H (1997) Cloning of human keratolinin cDNA: keratolinin is identical with a cysteine proteinase inhibitor, cystatin A, and is regulated by Ca²⁺, TPA and cAMP. J Invest Dermatol 108:843–847PubMed

14.

Steinert PM, Marekov LN (1995) The protein elafin, filaggrin, keratin intermediate filaments, loricrin, and small proline-rich protein 1 and 2 are isodipeptide cross-linked components of human epidermal cornified cell envelope. J Biol Chem 270:17702–17711PubMed

15.

Tezuka T, Qing J, Saheki M, Kusuda S, Takahashi M (1994) Terminal differentiation of facial epidermis of the aged: immunohistochemical studies. Dermatology 188:21–24PubMed

16.

Takahashi H, Asano K, Kinouchi M, Ishida-Yamamoto A, Wuepper KD, Iizuka H (1998) Structure and transcriptional regulation of human cystatin A gene: the 12-o-tetradecanoylphorbol-13-acetate (TPA) responsive element-2 site (−272 to −378) on cystatin A gene is critical for TPA-dependent regulation. J Biol Chem 273:17375–17380CrossRefPubMed

17.

Takahashi H, Honma M, Ishida-Yamamoto A, Namikawa K, Kiyama H, Iizuka H (2001) Human cystatin A expression of keratinocytes is positively regulated by Ras/MEKK1/MKK7/JNK signal transduction pathway and negatively regulated by Ras//Raf-1/MEK1ERK pathway. J Biol Chem 276:36632–36638CrossRefPubMed

18.

Hsieh J. Jurutka PW, Galligan MA, Terpening CM, Haussler CA, Samuels S, Shimizu Y, Shimizu N, Haussler MR (1991) Human vitamin D receptor is selectively phosphorylated by protein kinase C on serine 51, a residue crucial to its trans-activation function. Proc Natl Acad Sci U S A 88:9315–9319PubMed

19.

Mangelsdorf DJ, Ong ES, Dyck JA, Evans RM (1990) Nuclear receptor that identifies a novel retinoic acid response pathway. Nature 345:224–229PubMed

20.

Felgner PL, Gadek TR, Holm M, Roman R, Chan HW, Wenz M, Northrop JP, Ringold GM, Danielsen M (1987) Lipofection: a highly efficient, lipid-mediated DNA-transfected procedure. Proc Natl Acad Sci U S A 84:7413–7417PubMed

21.

Neuman JR, Morency CA, Russian KD (1987) A novel rapid assay for chloramphenicol acetyltransferase gene expression. Biotechniques 5:441

22.

Maniatis T, Fritsch EH, Sambrook T (1989) Molecular cloning: a laboratory manual, 2nd edn. Cold Spring Harbor Laboratory, Cold Spring Harbor, NY

23.

Robbins DJ, Zhen E, Owaki H, Vanderbilt CA, Ebert D, Geppert TD, Cobb MH (1993) Regulation and properties of extracellular signal-regulated protein kinase 1 and 2 in vitro. J Biol Chem 68:5097–5106

24.

Minden A, In A, McMahon M, Lange-Carter C, Derijard D, Davis RJ, Johnson GL, Karin M (1994) Differential activation of ERK and JNK mitogen-activated protein kinase by Raf-1 and MEKK. Science 266:1719–1723PubMed

25.

Yan M, Dai T, Deak JC, Kyriakis JM, Zon LI, Woodgett JR, Templeton DJ (1994) Activation of stress-activated protein kinase by MEKK1 phosphorylation of its activator SEK1. Nature 372:798–800PubMed

26.

Yan M, Templeton DJ (1994) Identification of 2 serine residues of MEK-1 that are differentially phosphorylated during activation by raf and MEK kinase. J Biol Chem 269:19067–19073PubMed

27.

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 20:2875–2886PubMed

28.

Miyake S, Makimura M, Kanegae Y, Harada S, Sato Y, Takamori K, Tokuda C, Saito I (1996) Efficient generation of recombinant adenoviruses using adenovirus DNA-terminal protein complex and cosmid bearing the full-length virus genome. Proc Natl Acad Sci U S A 93:1320–1324PubMed

29.

Niwa H, Yamamura K, Miyazaki J (1991) Efficient selection for high-expression transfectants with a novel eukaryotic vector. Gene108:193–199

30.

Kanegae Y, Makimura M, Saito I (1994) A simple and efficient method for purification of infectious recombinant adenovirus. Jpn J Med Sci Biol 47:157–166PubMed

31.

Zettergren JG, Peterson L, Wuepper KD (1984) Keratolinin: the soluble substrate of epidermal transglutaminase for human and bovine tissue. Proc Natl Acad Sci U S A 81:238–242PubMed

32.

Nakamura S, Takahashi H, Kinouchi M, Manabe A, Ishida-Yanmamoto A, Hashimoto Y, Iizuka H (2001) Differential phosphorylation of mitogen-activated protein kinase families by epidermal growth factor and ultraviolet B irradiation in SV40-transformed human keratinocytes. J Dermatol Sci 25:139–149CrossRefPubMed

33.

Komine M, Watabe Y, Shimaoka S, Sato F, Kake K, Nishina H, Ohtsuki M, Nakagawa H, Tamaki K (1999) The action of a novel vitamin D₃ analogue, OCT, on the immunomodulatory function of keratinocytes and lymphocytes. Arch Dermatol Res 291:500–506CrossRefPubMed

34.

Gniadecki R (1996) Stimulation versus inhibition of keratinocytes growth by 1,25-dihydroxyvitamin D₃: dependence on cell culture condition. J Invest Dermatol 106:510–516PubMed

35.

Hashimoto Y, Tsutsui M, Matsuo S, Iizuka S, Iizuka H (1995) Topical tacalcitol (1,24-(R)-dihydroxyvitamin D₃) induces a transient increase in thymidine incorporation and calmodulin content in pig epidermis following tape stripping in vivo. J Dermatol Sci 10:196–202CrossRefPubMed

36.

Chen A, Davis BH, Bissonnette M, Scaglione-Sewell B, Brasitus TA (1999) 1,25-dihydroxyvitamin D₃ stimulates activator protein-1-dependent Caco-2 cell differentiation. J Biol Chem 274:35505–35513CrossRefPubMed

37.

Sakai Y, Demay MB (2000) Evaluation of keratinocyte proliferation and differentiation in vitamin D₃ receptor knockout mice. Endocrinology 141:2043–2049PubMed

38.

Gniadecki R (1996) Activation of Raf-1-mitogen-activated protein kinase signaling pathway by 1,25-dihydroxyvitamin D₃ in normal human keratinocytes. J Invest Dermatol 106:1212–1217PubMed

39.

Wang X, Rao J, Studzinski P (2000) Inhibition of p38 MAP kinase activity up-regulates multiple MAP kinase pathway and potentiates 1,25-dihydroxyvitamin D₃-induced differentiation of human leukemia HL60 cells. Exp Cell Res 258:425–437CrossRefPubMed

40.

Matsumoto K, Azuma Y, Kiyoki M, Okumura H, Hashimoto K, Yoshikawa K (1991) Involvement of endogenously produced 1,25-dihydroxyvitamin D-3 in the growth and differentiation of human keratinocytes. Biochim Biophys Acta 1092:311–318PubMed

41.

Lutzow-Holm C, Heyden A, Huitfeldt HS, Brandtzaeg P, Clausen OPF (1995) Topical application of calcitriol alters expression of filaggrin but not keratin 1 in mouse epidermis. Arch Dermatol Res 287:480–487PubMed

42.

Takahashi H, Iizuka H (1993) Analysis of the 5′-upstream of human involucrin gene: activation by 12-o-tetradecanoylphorbol acetate. J Invest Dermatol 100:10–15PubMed

43.

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, AP-1 signal transduction pathway. J Biol Chem 273:24387–24395CrossRefPubMed

44.

Schmidt M, Goebeler M, Posern G, Feller SM, Seitz CS, Brocker EB, Rapp UR, Ludwig S (2000) Ras-independent activation of the Ras/MEK/ERK pathway upon calcium-induced differentiation of keratinocytes. J Biol Chem 275:41011–41017CrossRefPubMed

45.

Haase I, Hobbs RM, Romero MR, Broad S, Watt FM (2001) A role for mitogen-activated protein kinase activation by integrins in the pathogenesis of psoriasis. J Clin Invest 108:527–536CrossRefPubMed

Title: 1,25-Dihydroxyvitamin D3 increases human cystatin A expression by inhibiting the Raf-1/MEK1/ERK signaling pathway of keratinocytes
Authors: Hidetoshi Takahashi
Masaki Ibe
Masaru Honma
Akemi Ishida-Yamamoto
Yoshio Hashimoto
Hajime Iizuka
Publication date: 01-06-2003
Publisher: Springer-Verlag
Published in: Archives of Dermatological Research / Issue 2/2003
Print ISSN: 0340-3696
Electronic ISSN: 1432-069X
DOI: https://doi.org/10.1007/s00403-003-0396-5

Keynote webinar | Spotlight on medication adherence

Springer Medicine

1,25-Dihydroxyvitamin D₃ increases human cystatin A expression by inhibiting the Raf-1/MEK1/ERK signaling pathway of keratinocytes

Abstract

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 2/2003

Scatter factor regulation of integrin expression and function on oral epithelial cells

Ethanol and acetone stimulate the proliferation of HaCaT keratinocytes

Downregulation of tapasin expression in progressive human malignant melanoma

Meeting calender 295/2

Optical coherence tomography in contact dermatitis and psoriasis

Effects of 3-isobutyl-1-methylxanthine and kojic acid on cocultures and skin equivalents composed of HaCaT cells and human melanocytes