Palmitoyl‑RGD promotes the expression of dermal‑epidermal junction components in HaCaT cells

Lim,Joo Hyuck; Bae,Jung Soo; Lee,Seung Ki; Lee,Dong Hun

doi:10.3892/mmr.2022.12836

Palmitoyl‑RGD promotes the expression of dermal‑epidermal junction components in HaCaT cells

Authors:
- Joo Hyuck Lim
- Jung Soo Bae
- Seung Ki Lee
- Dong Hun Lee
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Affiliations: Biotechnology Research Institute, Research and Development Division, Celltrion Inc., Incheon 22014, Republic of Korea, Department of Dermatology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul National University, Seoul 03080, Republic of Korea
Published online on: August 29, 2022 https://doi.org/10.3892/mmr.2022.12836
Article Number: 320

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Abstract

With age, the dermal‑epidermal junction (DEJ) becomes thinner and production of its protein components decreases; this may be associated with increased fragility and wrinkling of skin. Topical treatment with palmitoyl‑Arg‑Gly‑Asp (PAL‑RGD) improves facial wrinkles, skin elasticity and dermal density in humans. In the present study, the effect of PAL‑RGD on expression of DEJ components, such as laminin and collagen, was assessed. Human HaCaT keratinocytes were treated with PAL‑RGD. The protein expression levels of laminin‑332, collagen IV and collagen XVII were examined by western blotting. Reverse transcription-quantitative PCR was used to analyze laminin subunit (LAM)A3, LAMB3, LAMC2, collagen type IV α 1 chain (COL4A1) and COL17A1 mRNA expression levels. Western blot analysis showed that the expression levels of proteins comprising the DEJ, including laminin α3, β3 and γ2 and collagen IV and XVII demonstrated a significant dose‑dependent increase following PAL‑RGD treatment. Furthermore, PAL‑RGD treatment significantly enhanced LAMA3, LAMB3, LAMC2, COL4A1 and COL17A1 mRNA expression levels. PAL‑RGD may enhance the DEJ by inducing the expression of laminin‑332, collagen IV and collagen XVII.

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1	Burgeson RE and Christiano AM: The dermal-epidermal junction. Curr Opin Cell Biol. 9:651–658. 1997. View Article : Google Scholar : PubMed/NCBI
2	Roig-Rosello E and Rousselle P: The human epidermal basement membrane: A shaped and cell instructive platform that aging slowly alters. Biomolecules. 10:16072020. View Article : Google Scholar : PubMed/NCBI
3	Marionnet C, Vioux-Chagnoleau C, Pierrard C, Sok J, Asselineau D and Bernerd F: Morphogenesis of dermal-epidermal junction in a model of reconstructed skin: Beneficial effects of vitamin C. Exp Dermatol. 15:625–633. 2006. View Article : Google Scholar : PubMed/NCBI
4	Lavker RM, Zheng P and Dong G: Aged skin: A study by light, transmission electron, and scanning electron microscopy. J Invest Dermatol. 88 (3 Suppl):44s–51s. 1987. View Article : Google Scholar : PubMed/NCBI
5	Vázquez F, Palacios S, Alemañ N and Guerrero F: Changes of the basement membrane and type IV collagen in human skin during aging. Maturitas. 25:209–215. 1996. View Article : Google Scholar : PubMed/NCBI
6	Langton AK, Halai P, Griffiths CE, Sherratt MJ and Watson RE: The impact of intrinsic ageing on the protein composition of the dermal-epidermal junction. Mech Ageing Dev. 156:14–16. 2016. View Article : Google Scholar : PubMed/NCBI
7	Mondon P, Hillion M, Peschard O, Andre N, Marchand T, Doridot E, Feuilloley MG, Pionneau C and Chardonnet S: Evaluation of dermal extracellular matrix and epidermal-dermal junction modifications using matrix-assisted laser desorption/ionization mass spectrometric imaging, in vivo reflectance confocal microscopy, echography, and histology: Effect of age and peptide applications. J Cosmet Dermatol. 14:152–160. 2015. View Article : Google Scholar : PubMed/NCBI
8	Contet-Audonneau JL, Jeanmaire C and Pauly G: A histological study of human wrinkle structures: Comparison between sun-exposed areas of the face, with or without wrinkles, and sun-protected areas. Br J Dermatol. 140:1038–1047. 1999. View Article : Google Scholar : PubMed/NCBI
9	Varlet BL, Chaudagne C, Barré P, Sauvage C, Berthouloux B, Meybeck A, Dumas M, Saunois A and Bonté F: Age-related functional and structural changes in human dermo-epidermal junction components. Journal of Investigative Dermatology Symposium Proceedings. Vol. 3. Elsevier; pp. 172–179. 1998, View Article : Google Scholar : PubMed/NCBI
10	Ishihara J, Ishihara A, Fukunaga K, Sasaki K, White MJV, Briquez PS and Hubbell JA: Laminin heparin-binding peptides bind to several growth factors and enhance diabetic wound healing. Nat Commun. 9:21632018. View Article : Google Scholar : PubMed/NCBI
11	Iorio V, Troughton LD and Hamill KJ: Laminins: Roles and utility in wound repair. Adv Wound Care (New Rochelle). 4:250–263. 2015. View Article : Google Scholar : PubMed/NCBI
12	Chung HJ and Uitto J: Type VII collagen: The anchoring fibril protein at fault in dystrophic epidermolysis bullosa. Dermatol Clin. 28:93–105. 2010. View Article : Google Scholar : PubMed/NCBI
13	Watanabe M, Natsuga K, Nishie W, Kobayashi Y, Donati G, Suzuki S, Fujimura Y, Tsukiyama T, Ujiie H, Shinkuma S, et al: Type XVII collagen coordinates proliferation in the interfollicular epidermis. Elife. 6:e266352017. View Article : Google Scholar : PubMed/NCBI
14	Jeong S, Yoon S, Kim S, Jung J, Kor M, Shin K, Lim C, Han HS, Lee H, Park KY, et al: Anti-wrinkle benefits of peptides complex stimulating skin basement membrane proteins expression. Int J Mol Sci. 21:732019. View Article : Google Scholar : PubMed/NCBI
15	Amano S: Possible involvement of basement membrane damage in skin photoaging. Journal of Investigative Dermatology Symposium Proceedings. Vol. 14. Elsevier; pp. 2–7. 2009, View Article : Google Scholar : PubMed/NCBI
16	Kusumaningrum N, Oh JH, Lee DH, Shin CY, Jang JH, Kim YK and Chung JH: Topical treatment with a cathepsin G inhibitor, β-keto-phosphonic acid, blocks ultraviolet irradiation-induced basement membrane damage in hairless mouse skin. Photodermatol Photoimmunol Photomed. 35:148–156. 2019. View Article : Google Scholar : PubMed/NCBI
17	Bae JS, Kim JM, Kim JY, Choi CH, Kim JY, Moon WK, Lee MS, Moon SH, Lim JH, Park SJ, et al: Topical application of palmitoyl-RGD reduces human facial wrinkle formation in Korean women. Arch Dermatol Res. 309:665–671. 2017. View Article : Google Scholar : PubMed/NCBI
18	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(−Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI
19	Peters BP, Hartle RJ, Krzesicki RF, Kroll TG, Perini F, Balun JE, Goldstein IJ and Ruddon RW: The biosynthesis, processing, and secretion of laminin by human choriocarcinoma cells. J Biol Chem. 260:14732–1442. 1985. View Article : Google Scholar : PubMed/NCBI
20	Korang K, Christiano AM, Uitto J and Mauviel A: Differential cytokine modulation of the genes LAMA3, LAMB3, and LAMC2, encoding the constitutive polypeptides, alpha 3, beta 3, and gamma 2, of human laminin 5 in epidermal keratinocytes. FEBS Lett. 368:556–558. 1995. View Article : Google Scholar : PubMed/NCBI
21	Feru J, Delobbe E, Ramont L, Brassart B, Terryn C, Dupont-Deshorgue A, Garbar C, Monboisse JC, Maquart FX and Brassart-Pasco S: Aging decreases collagen IV expression in vivo in the dermo-epidermal junction and in vitro in dermal fibroblasts: Possible involvement of TGF-β1. Eur J Dermatol. 26:350–360. 2016. View Article : Google Scholar : PubMed/NCBI
22	Huilaja L, Hurskainen T, Autio-Harmainen H, Hofmann SC, Sormunen R, Räsänen J, Ilves M, Franzke CW, Bruckner-Tuderman L and Tasanen K: Pemphigoid gestationis autoantigen, transmembrane collagen XVII, promotes the migration of cytotrophoblastic cells of placenta and is a structural component of fetal membranes. Matrix Biol. 27:190–200. 2008. View Article : Google Scholar : PubMed/NCBI
23	Sugawara K, Tsuruta D, Ishii M, Jones JC and Kobayashi H: Laminin-332 and −511 in skin. Exp Dermatol. 17:473–480. 2008. View Article : Google Scholar : PubMed/NCBI
24	Miner JH and Yurchenco PD: Laminin functions in tissue morphogenesis. Annu Rev Cell Dev Biol. 20:255–284. 2004. View Article : Google Scholar : PubMed/NCBI
25	Tsuruta D, Kobayashi H, Imanishi H, Sugawara K, Ishii M and Jones JC: Laminin-332-integrin interaction: A target for cancer therapy? Curr Med Chem. 15:1968–1975. 2008. View Article : Google Scholar : PubMed/NCBI
26	Kariya Y and Gu J: Roles of laminin-332 and alpha6beta4 integrin in tumor progression. Mini Rev Med Chem. 9:1284–1291. 2009. View Article : Google Scholar : PubMed/NCBI
27	Gonzales M, Haan K, Baker SE, Fitchmun M, Todorov I, Weitzman S and Jones JC: A cell signal pathway involving laminin-5, alpha3beta1 integrin, and mitogen-activated protein kinase can regulate epithelial cell proliferation. Mol Biol Cell. 10:259–270. 1999. View Article : Google Scholar : PubMed/NCBI
28	Choma DP, Milano V, Pumiglia KM and DiPersio CM: Integrin alpha3beta1-dependent activation of FAK/Src regulates Rac1-mediated keratinocyte polarization on laminin-5. J Invest Dermatol. 127:31–40. 2007. View Article : Google Scholar : PubMed/NCBI
29	Mainiero F, Pepe A, Wary KK, Spinardi L, Mohammadi M, Schlessinger J and Giancotti F: Signal transduction by the alpha 6 beta 4 integrin: Distinct beta 4 subunit sites mediate recruitment of Shc/Grb2 and association with the cytoskeleton of hemidesmosomes. EMBO J. 14:4470–4481. 1995. View Article : Google Scholar : PubMed/NCBI
30	Pöschl E, Schlötzer-Schrehardt U, Brachvogel B, Saito K, Ninomiya Y and Mayer U: Collagen IV is essential for basement membrane stability but dispensable for initiation of its assembly during early development. Development. 131:1619–1628. 2004. View Article : Google Scholar : PubMed/NCBI
31	Brown KL, Cummings CF, Vanacore RM and Hudson BG: Building collagen IV smart scaffolds on the outside of cells. Protein Sci. 26:2151–2161. 2017. View Article : Google Scholar : PubMed/NCBI
32	Good MC, Zalatan JG and Lim WA: Scaffold proteins: Hubs for controlling the flow of cellular information. Science. 332:680–686. 2011. View Article : Google Scholar : PubMed/NCBI
33	Trappmann B, Gautrot JE, Connelly JT, Strange DG, Li Y, Oyen ML, Cohen Stuart MA, Boehm H, Li B, Vogel V, et al: Extracellular-matrix tethering regulates stem-cell fate. Nat Mater. 11:642–649. 2012. View Article : Google Scholar : PubMed/NCBI
34	Nishimura M, Nishie W, Shirafuji Y, Shinkuma S, Natsuga K, Nakamura H, Sawamura D, Iwatsuki K and Shimizu H: Extracellular cleavage of collagen XVII is essential for correct cutaneous basement membrane formation. Hum Mol Genet. 25:328–339. 2016. View Article : Google Scholar : PubMed/NCBI
35	Natsuga K, Watanabe M, Nishie W and Shimizu H: Life before and beyond blistering: The role of collagen XVII in epidermal physiology. Exp Dermatol. 28:1135–1141. 2019. View Article : Google Scholar : PubMed/NCBI
36	Kamaguchi M, Iwata H, Nishie W, Toyonaga E, Ujiie H, Natsuga K, Kitagawa Y and Shimizu H: The direct binding of collagen XVII and collagen IV is disrupted by pemphigoid autoantibodies. Lab Invest. 99:48–57. 2019. View Article : Google Scholar : PubMed/NCBI