Differentially‑expressed genes identified by suppression subtractive hybridization in the bone marrow hematopoietic stem cells of patients with psoriasis

Zhang,Zhenying; Yu,Zhen; Tian,Pan; Hou,Suchun; Han,Shixin; Tan,Xuejing; Piao,Yongjun; Liu,Xiaoming

doi:10.3892/mmr.2014.2203

Differentially‑expressed genes identified by suppression subtractive hybridization in the bone marrow hematopoietic stem cells of patients with psoriasis

Authors:
- Zhenying Zhang
- Zhen Yu
- Pan Tian
- Suchun Hou
- Shixin Han
- Xuejing Tan
- Yongjun Piao
- Xiaoming Liu
View Affiliations

Affiliations: Department of Dermatology, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116023, P.R. China, Dalian Dermatosis Hospital, Dalian, Liaoning, P.R. China, Department of Dermatology, Hong Kong University-Shenzhen Hospital, Shenzhen, Guangdong 518053, P.R. China
Published online on: May 2, 2014 https://doi.org/10.3892/mmr.2014.2203
Pages: 479-485

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Psoriasis is a T cell‑mediated, chronic, relapsing and inflammatory cutaneous disorder. The dysfunctional activity of T cells in patients with psoriasis is attributed to bone marrow hematopoietic stem cells (BMHSCs). To understand the pathogenic roles of BMHSCs in psoriasis, a differential gene expression analysis was performed using suppression subtractive hybridization of the BMHSCs from a patient with psoriasis and a healthy control. Using a cDNA array dot blot screening to screen 600 genes from forward‑ and reverse‑subtracted cDNA libraries, 17 differentially‑expressed sequence tags (ESTs) were identified. The genes within the ESTs were observed to be the homologs of genes that are involved in various cellular processes, including hormone signaling, RNA catabolism, protein ADP DNA base melting, transcriptional regulation, cell cycle regulation and metabolism. CD45, which was overexpressed in the psoriatic BMHSCs, was further analyzed using relative quantitative polymerase chain reaction. In addition, the levels of CD45 in the peripheral blood cells (PBCs) of the patients with psoriasis were markedly increased and closely associated with disease severity. An abnormality of hematopoietic progenitor cells, e.g., CD45 overexpression, may be transferred to PBCs via hematopoiesis, and may account for the psoriasis‑inducing properties of activated T cells.

View Figures

View References

1	Nickoloff BJ: The immunologic and genetic basis of psoriasis. Arch Dermatol. 135:1104–1110. 2000.PubMed/NCBI
2	Sabat R, Philipp S, Höflich C, et al: Immunopathogenesis of psoriasis. Exp Dermatol. 16:779–798. 2007. View Article : Google Scholar
3	van Lingen RG, van de Kerkhof PC, de Jong EM, et al: Reduced CD26 bright expression of peripheral blood CD8+ T-cell subsets in psoriatic patients. Exp Dermatol. 17:343–348. 2008.PubMed/NCBI
4	Berth-Jones J: The use of ciclosporin in psoriasis. J Dermatolog Treat. 16:258–277. 2005. View Article : Google Scholar
5	Krueger JG, Wolfe JT, Nabeya RT, et al: Successful ultraviolet B treatment of psoriasis is accompanied by a reversal of keratinocyte pathology and by selective depletion of intraepidermal T cells. J Exp Med. 182:2057–2068. 1995. View Article : Google Scholar : PubMed/NCBI
6	Gottlieb SL, Gilleaudeau P, Johnson R, et al: Response of psoriasis to a lymphocyte-selective toxin (DAB389IL-2) suggests a primary immune, but not keratinocyte, pathogenic basis. Nat Med. 1:442–447. 1995. View Article : Google Scholar : PubMed/NCBI
7	Abrams JR, Kelley SL, Hayes E, et al: Blockade of T lymphocyte costimulation with cytotoxic T lymphocyte-associated antigen 4-immunoglobulin (CTLA4Ig) reverses the cellular pathology of psoriatic plaques, including the activation of keratinocytes, dendritic cells, and endothelial cells. J Exp Med. 192:681–694. 2000. View Article : Google Scholar
8	Gordon KB, Papp KA, Hamilton TK, et al: Efalizumab for patients with moderate to severe plaque psoriasis: a randomized controlled trial. JAMA. 290:3073–3080. 2003. View Article : Google Scholar : PubMed/NCBI
9	Tomfohrde J, Silverman A, Barnes R, et al: Gene for familial psoriasis susceptibility mapped to the distal end of human chromosome 17q. Science. 264:1141–1145. 1994. View Article : Google Scholar : PubMed/NCBI
10	Hüffmeier U, Steffens M, Burkhardt H, et al: Evidence for susceptibility determinant(s) to psoriasis vulgaris in or near PTPN22 in German patients. J Med Genet. 43:517–522. 2006.PubMed/NCBI
11	Bowcock AM: The genetics of psoriasis and autoimmunity. Annu Rev Genomics Hum Genet. 6:93–122. 2005. View Article : Google Scholar : PubMed/NCBI
12	Galić Z, Kitchen SG, Subramanian A, et al: Generation of T lineage cells from human embryonic stem cells in a feeder free System. Stem Cells. 27:100–107. 2009.PubMed/NCBI
13	Kondo M, Weissman IL and Akashi K: Identification of clonogenic common lymphoid progenitors in mouse bone marrow. Cell. 91:661–672. 1997. View Article : Google Scholar : PubMed/NCBI
14	Petrie HT and Zúñiga-Pflücker JC: Zoned out: functional mapping of stromal signaling microenvironments in the thymus. Annu Rev Immunol. 25:649–679. 2007. View Article : Google Scholar : PubMed/NCBI
15	Petrie HT: Cell migration and the control of post-natal T-cell lymphopoiesis in the thymus. Nat Rev Immunol. 3:859–866. 2003. View Article : Google Scholar : PubMed/NCBI
16	Zhang K, Li X, Yin G, et al: Functional characterization of T cells differentiated in vitro from bone marrow-derived CD34 cells of psoriatic patients with family history. Exp Dermatol. 19:e128–e135. 2010. View Article : Google Scholar : PubMed/NCBI
17	Zhang K, Zhang R, Li X, et al: The mRNA expression and promoter methylation status of the p16 gene in colony-forming cells with high proliferative potential in patients with psoriasis. Clin Exp Dermatol. 32:702–708. 2007. View Article : Google Scholar : PubMed/NCBI
18	Lacaud G, Gore L, Kennedy M, et al: Runx1 is essential for hematopoietic commitment at the hemangioblast stage of development in vitro. Blood. 100:458–466. 2002. View Article : Google Scholar : PubMed/NCBI
19	Helms C, Cao L, Krueger JG, et al: A putative RUNX1 binding site variant between SLC9A3R1 and NAT9 is associated with susceptibility to psoriasis. Nat Genet. 35:349–356. 2003. View Article : Google Scholar : PubMed/NCBI
20	Kanamori H, Tanaka M, Kawaguchi H, et al: Resolution of psoriasis following allogeneic bone marrow transplantation for chronic myelogenous leukemia: case report and review of the literature. Am J Hematol. 71:41–44. 2002. View Article : Google Scholar : PubMed/NCBI
21	Woods AC and Mant MJ: Amelioration of severe psoriasis with psoriatic arthritis for 20 years after allogeneic haematopoietic stem cell transplantation. Ann Rheum Dis. 65:6972006.PubMed/NCBI
22	Snowden JA and Heaton DC: Development of psoriasis after syngeneic bone marrow transplant from psoriatic donor: further evidence for adoptive autoimmunity. Br J Dermatol. 137:130–132. 1997. View Article : Google Scholar : PubMed/NCBI
23	Byth KF, Conroy LA, Howlett S, et al: CD45-null transgenic mice reveal a positive regulatory role for CD45 in early thymocyte development, in the selection of CD4+CD8+thymocytes, and B cell maturation. J Exp Med. 183:1707–1718. 1996.PubMed/NCBI
24	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(−Delta Delta C(T)). Method. 25:402–408. 2001.
25	Ward V, Hennig BJ, Hirai K, et al: Geographical distribution and disease associations of the CD45 exon 6 138G variant. Immunogenetics. 58:235–239. 2006. View Article : Google Scholar : PubMed/NCBI
26	Kishihara K, Penninger J, Wallace VA, et al: Normal B lymphocyte development but impaired T cell maturation in CD45-exon6 protein tyrosine phosphatase-deficient mice. Cell. 74:143–156. 1993. View Article : Google Scholar : PubMed/NCBI
27	Hermiston ML, Xu Z and Weiss A: CD45: a critical regulator of signaling thresholds in immune cells. Annu Rev Immunol. 21:107–137. 2003. View Article : Google Scholar : PubMed/NCBI
28	Pingel JT and Thomas ML: Evidence that the leukocyte-common antigen is required for antigen-induced T lymphocyte proliferation. Cell. 58:1055–1065. 1989. View Article : Google Scholar : PubMed/NCBI
29	Weaver CT, Pingel JT, Nelson JO, et al: CD8+ T-cell clones dificient in the expression of the CD45 protein tyrosine phosphatase have impaired responses to T-cell receptor stimuli. Mol Cell Biol. 11:4415–4422. 1991.
30	Koretzky GA, Kohmetscher MA, Kadleck T, et al: Restoration of T cell receptor-mediated signal transduction by transfection of CD45 cDNA into a CD45-deficient variant of the Jurkat T cell line. J Immunol. 149:1138–1142. 1992.PubMed/NCBI
31	Montoya M, Dawes R, Reid D, Lee LN, Piercy J, Borrow P, Tchilian EZ and Beverley PC: CD45 is required for type I IFN production by dendritic cells. Eur J Immunol. 36:2150–2158. 2006. View Article : Google Scholar : PubMed/NCBI
32	Shen F, Xu XL, Graf LH, et al: CD45-cross-linking stimulates IFN-gamma production in NK cells. J Immunol. 154:644–652. 1995.PubMed/NCBI
33	Dawes R, Petrova S, Liu Z, et al: Combinations of CD45 isoforms are crucial for immune function and disease. J Immunol. 176:3417–3425. 2006. View Article : Google Scholar : PubMed/NCBI
34	Takahashi H, Tsuji H, Hashimoto Y, Ishida-Yamamoto A and Iizuka H: Serum cytokines and growth factor levels in Japanese patients with psoriasis. Clin Exp Dermatol. 35:645–649. 2010. View Article : Google Scholar : PubMed/NCBI
35	Szegedi A, Aleksza M, Gonda A, et al: Elevated rate of Thelper1 (T(H)1) lymphocytes and serum IFN-gamma levels in psoriatic patients. Immunol Lett. 86:277–280. 2003. View Article : Google Scholar : PubMed/NCBI
36	Arican Ozer, Aral Murat, Sasmaz Sezai, et al: Serum levels of TNF-alpha, IFN-gamma, IL-6, IL-8, IL-12, IL-17, and IL-18 in patients with active psoriasis and correlation with disease severity. Mediators Inflamm. 24:273–279. 2005. View Article : Google Scholar : PubMed/NCBI
37	Zhang K, Zhang R, Li X, et al: Promoter methylation status of p15 and p21 genes in HPP-CFCs of bone marrow of patients with psoriasis. Eur J Dermatol. 9:141–146. 2009.PubMed/NCBI
38	Yin G, Li J, Wan Y, et al: Abnormality of RUNX1 signal transduction in psoriatic CD34+ bone marrow cells. Br J Dermatol. 164:1043–1051. 2011.PubMed/NCBI