Transcriptome sequencing revealed candidate genes relevant to mesenchymal stem cells' role in aortic dissection patients

Yang,Junlin; Zou,Sili; Liao,Mingfang; Qu,Lefeng

doi:10.3892/mmr.2017.7851

Transcriptome sequencing revealed candidate genes relevant to mesenchymal stem cells' role in aortic dissection patients

Authors:
- Junlin Yang
- Sili Zou
- Mingfang Liao
- Lefeng Qu
View Affiliations

Affiliations: Department of Vascular Surgery, Changzheng Hospital, Shanghai 200003, P.R. China
Published online on: October 20, 2017 https://doi.org/10.3892/mmr.2017.7851
Pages: 273-283
Copyright: © Yang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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

Aortic dissection (AD) results from the imbalance between synthesis and degradation of extracellular matrices in aortic wall, which is characterized by chronic inflammation. Mesenchymal stem cells (MSCs) are known for anti‑inflammatory and repairing effects and have therefore been studied for treatment for numerous diseases, including AD. However, it is unclear which genes or signaling pathways contribute to MSCs' role in AD. In the present study, RNA sequencing (RNA‑seq) was conducted between MSCs from patients with AS (AD‑MSCs) and those from age‑matched healthy donors (HD‑MSCs). RNA‑seq revealed 201 differentially expressed genes (DEGs) under the filter of fold change>2 and P‑value <0.05, in which 93 genes were upregulated and 108 downregulated. We selectively verified 9 out of 201 DEGs via reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR) with an enlarged sample size. The trends of RT‑qPCR results were consistent with RNA‑seq data. Unsupervised hierarchical clustering of the 9‑gene expression profiles enables the division of clinical samples into AD and HD groups. Kyoto Encyclopedia of Genes and Genomes analysis displayed a significant change in adhesion‑related signaling pathways in AD‑MSCs compared with HD‑MSCs, whereas gene ontology analysis demonstrated DEGs were enriched in functions associated with development and morphogenesis, from a functional perspective. The present results indicate that gene expression profiles of AD‑MSCs were significantly changed compared with HD‑MSCs. These changes are probably associated with MSCs' adhesion capacity and development. These results may provide important insights into the role of MSCs in AD pathogenesis.

View Figures

View References

1	Hagan PG, Nienaber CA, Isselbacher EM, Bruckman D, Karavite DJ, Russman PL, Evangelista A, Fattori R, Suzuki T, Oh JK, et al: The International Registry of Acute Aortic Dissection (IRAD): New insights into an old disease. JAMA. 283:897–903. 2000. View Article : Google Scholar : PubMed/NCBI
2	Schlatmann TJ and Becker AE: Pathogenesis of dissecting aneurysm of aorta. Comparative histopathologic study of significance of medial changes. Am J Cardiol. 39:21–26. 1977. View Article : Google Scholar : PubMed/NCBI
3	López-Candales A, Holmes DR, Liao S, Scott MJ, Wickline SA and Thompson RW: Decreased vascular smooth muscle cell density in medial degeneration of human abdominal aortic aneurysms. Am J Pathol. 150:993–1007. 1997.PubMed/NCBI
4	De Bruin JL, Baas AF, Buth J, Prinssen M, Verhoeven EL, Cuypers PW, van Sambeek MR, Balm R, Grobbee DE and Blankensteijn JD: DREAM Study Group: Long-term outcome of open or endovascular repair of abdominal aortic aneurysm. N Engl J Med. 362:1881–1889. 2010. View Article : Google Scholar : PubMed/NCBI
5	SVN Task Force for Clinical Practice Guideline: 2009 Clinical practice guideline for patients undergoing endovascular repair of abdominal aortic aneurysms (AAA). J Vasc Nurs. 27:48–63. 2009. View Article : Google Scholar : PubMed/NCBI
6	Nabel EG, Yang Z, Liptay S, San H, Gordon D, Haudenschild CC and Nabel GJ: Recombinant platelet-derived growth factor B gene expression in porcine arteries induce intimal hyperplasia in vivo. J Clin Invest. 91:1822–1829. 1993. View Article : Google Scholar : PubMed/NCBI
7	Phinney DG and Prockop DJ: Concise review: Mesenchymal stem/multipotent stromal cells: The state of transdifferentiation and modes of tissue repair-current views. Stem Cells. 25:2896–2902. 2007. View Article : Google Scholar : PubMed/NCBI
8	Hashizume R, Yamawaki-Ogata A, Ueda Y, Wagner WR and Narita Y: Mesenchymal stem cells attenuate angiotensin II-induced aortic aneurysm growth in apolipoprotein E-deficient mice. J Vasc Surg. 54:1743–1752. 2011. View Article : Google Scholar : PubMed/NCBI
9	Schneider F, Saucy F, de Blic R, Dai J, Mohand F, Rouard H, Ricco JB, Becquemin JP, Gervais M and Allaire E: Bone marrow mesenchymal stem cells stabilize already-formed aortic aneurysms more efficiently than vascular smooth muscle cells in a rat model. Eur J Vasc Endovasc Surg. 45:666–672. 2013. View Article : Google Scholar : PubMed/NCBI
10	Davis JP, Salmon M, Pope NH, Lu G, Su G, Sharma AK, Ailawadi G and Upchurch GR Jr: Attenuation of aortic aneurysms with stem cells from different genders. J Surg Res. 199:249–258. 2015. View Article : Google Scholar : PubMed/NCBI
11	Zou S, Ren P, Zhang L, Azares AR, Zhang S, Coselli JS, Shen YH and LeMaire SA: AKT2 promotes bone marrow cell-mediated aortic protection in mice. Ann Thorac Surg. 101:2085–2096. 2016. View Article : Google Scholar : PubMed/NCBI
12	Shen YH, Hu X, Zou S, Wu D, Coselli JS and LeMaire SA: Stem cells in thoracic aortic aneurysms and dissections: Potential contributors to aortic repair. Ann Thorac Surg. 93:1524–1533. 2012. View Article : Google Scholar : PubMed/NCBI
13	Xie J, Jones TJ, Feng D, Cook TG, Jester AA, Yi R, Jawed YT, Babbey C, March KL and Murphy MP: Human adipose-derived stem cells suppress elastase-induced murine abdominal aortic inflammation and aneurysm expansion through paracrine factors. Cell Transplant. 26:173–189. 2017. View Article : Google Scholar : PubMed/NCBI
14	Sharma AK, Salmon MD, Lu G, Su G, Pope NH, Smith JR, Weiss ML and Upchurch GR Jr: Mesenchymal stem cells attenuate NADPH oxidase-dependent high mobility group box 1 production and inhibit abdominal aortic aneurysms. Arterioscler Thromb Vasc Biol. 36:908–918. 2016. View Article : Google Scholar : PubMed/NCBI
15	del Moral Riera L, Largo C, Ramirez JR, Vega Clemente L, Heredero Fernández A, de Cubas Riera L, Garcia-Olmo D and Garcia-Arranz M: Potential of mesenchymal stem cell in stabilization of abdominal aortic aneurysm sac. J Surg Res. 195:325–333. 2015. View Article : Google Scholar : PubMed/NCBI
16	Ciavarella C, Alviano F, Gallitto E, Ricci F, Buzzi M, Velati C, Stella A, Freyrie A and Pasquinelli G: Human vascular wall mesenchymal stromal cells contribute to abdominal aortic aneurysm pathogenesis through an impaired immunomodulatory activity and increased levels of matrix metalloproteinase-9. Circ J. 79:1460–1469. 2015. View Article : Google Scholar : PubMed/NCBI
17	Dominici M, Le Blanc K, Mueller I, Slaper-Cortenbach I, Marini F, Krause D, Deans R, Keating A, Prockop Dj and Horwitz E: Minimal criteria for defining multipotent mesenchymal stromal cells. The international society for cellular therapy position statement. Cytotherapy. 8:315–317. 2006. View Article : Google Scholar : PubMed/NCBI
18	Nicoletti I, Migliorati G, Pagliacci MC, Grignani F and Riccardi C: A rapid and simple method for measuring thymocyte apoptosis by propidium iodide staining and flow cytometry. J Immunol Methods. 139:271–279. 1991. View Article : Google Scholar : PubMed/NCBI
19	Longo GM, Xiong W, Greiner TC, Zhao Y, Fiotti N and Baxter BT: Matrix metalloproteinases 2 and 9 work in concert to produce aortic aneurysms. J Clin Invest. 110:625–632. 2002. View Article : Google Scholar : PubMed/NCBI
20	Hackam DG, Thiruchelvam D and Redelmeier DA: Angiotensin-converting enzyme inhibitors and aortic rupture: A population-based case-control study. Lancet. 368:659–665. 2006. View Article : Google Scholar : PubMed/NCBI
21	Schouten O, van Laanen JH, Boersma E, Vidakovic R, Feringa HH, Dunkelgrün M, Bax JJ, Koning J, van Urk H and Poldermans D: Statins are associated with a reduced infrarenal abdominal aortic aneurysm growth. Eur J Vasc Endovasc Surg. 32:21–26. 2006. View Article : Google Scholar : PubMed/NCBI
22	Yamawaki-Ogata A, Hashizume R, Satake M, Kaneko H, Mizutani S, Moritan T, Ueda Y and Narita Y: A doxycycline loaded, controlled-release, biodegradable fiber for the treatment of aortic aneurysms. Biomaterials. 31:9554–9564. 2010. View Article : Google Scholar : PubMed/NCBI
23	Baxter BT, Pearce WH, Waltke EA, Littooy FN, Hallett JW Jr, Kent KC, Upchurch GR Jr, Chaikof EL, Mills JL, Fleckten B, et al: Prolonged administration of doxycycline in patients with small asymptomatic abdominal aortic aneurysms: Report of a prospective (Phase II) multicenter study. J Vasc Surg. 36:1–12. 2002. View Article : Google Scholar : PubMed/NCBI
24	Walton LJ, Franklin IJ, Bayston T, Brown LC, Greenhalgh RM, Taylor GW and Powell JT: Inhibition of prostaglandin E2 synthesis in abdominal aortic aneurysms: Implications for smooth muscle cell viability, inflammatory processes, and the expansion of abdominal aortic aneurysms. Circulation. 100:48–54. 1999. View Article : Google Scholar : PubMed/NCBI
25	Yoshimura K, Aoki H, Ikeda Y, Fujii K, Akiyama N, Furutani A, Hoshii Y, Tanaka N, Ricci R, Ishihara T, et al: Regression of abdominal aortic aneurysm by inhibition of c-Jun N-terminal kinase. Nat Med. 11:1330–1338. 2005. View Article : Google Scholar : PubMed/NCBI
26	Bianco P, Riminucci M, Gronthos S and Robey PG: Bone marrow stromal stem cells: Nature, biology, and potential applications. Stem Cells. 19:180–192. 2001. View Article : Google Scholar : PubMed/NCBI
27	Matsumura G, Miyagawa-Tomita S, Shin'oka T, Ikada Y and Kurosawa H: First evidence that bone marrow cells contribute to the construction of tissue-engineered vascular autografts in vivo. Circulation. 108:1729–1734. 2003. View Article : Google Scholar : PubMed/NCBI
28	Allaire E, Muscatelli-Groux B, Guinault AM, Pages C, Goussard A, Mandet C, Bruneval P, Méllière D and Becquemin JP: Vascular smooth muscle cell endovascular therapy stabilizes already developed aneurysms in a model of aortic injury elicited by inflammation and proteolysis. Ann Surg. 239:417–427. 2004. View Article : Google Scholar : PubMed/NCBI
29	Sata M, Saiura A, Kunisato A, Tojo A, Okada S, Tokuhisa T, Hirai H, Makuuchi M, Hirata Y and Nagai R: Hematopoietic stem cells differentiate into vascular cells that participate in the pathogenesis of atherosclerosis. Nat Med. 8:403–409. 2002. View Article : Google Scholar : PubMed/NCBI
30	Saiura A, Sata M, Hirata Y, Nagai R and Makuuchi M: Circulating smooth muscle progenitor cells contribute to atherosclerosis. Nat Med. 7:382–383. 2001. View Article : Google Scholar : PubMed/NCBI
31	Ryu JH, Park M, Kim BK, Ryu KH and Woo SY: Tonsil-derived mesenchymal stromal cells produce CXCR2-binding chemokines and acquire follicular dendritic cell-like phenotypes under TLR3 stimulation. Cytokine. 73:225–235. 2015. View Article : Google Scholar : PubMed/NCBI
32	Veréb Z, Póliska S, Albert R, Olstad OK, Boratkó A, Csortos C, Moe MC, Facskó A and Petrovski G: Role of human corneal stroma-derived mesenchymal-like stem cells in corneal immunity and wound healing. Sci Rep. 6:262272016. View Article : Google Scholar : PubMed/NCBI
33	Li Q, Guo Y, Chen F, Liu J and Jin P: Stromal cell-derived factor-1 promotes human adipose tissue-derived stem cell survival and chronic wound healing. Exp Ther Med. 12:45–50. 2016. View Article : Google Scholar : PubMed/NCBI
34	Sharma AK, Lu G, Jester A, Johnston WF, Zhao Y, Hajzus VA, Saadatzadeh MR, Su G, Bhamidipati CM, Mehta GS, et al: Experimental abdominal aortic aneurysm formation is mediated by IL-17 and attenuated by mesenchymal stem cell treatment. Circulation. 126 11 Suppl 1:S38–S45. 2012. View Article : Google Scholar : PubMed/NCBI
35	Iida Y, Xu B, Xuan H, Glover KJ, Tanaka H, Hu X, Fujimura N, Wang W, Schultz JR, Turner CR and Dalman RL: Peptide inhibitor of CXCL4-CCL5 heterodimer formation, MKEY, inhibits experimental aortic aneurysm initiation and progression. Arterioscler Thromb Vasc Biol. 33:718–726. 2013. View Article : Google Scholar : PubMed/NCBI
36	Anzai A, Shimoda M, Endo J, Kohno T, Katsumata Y, Matsuhashi T, Yamamoto T, Ito K, Yan X, Shirakawa K, et al: Adventitial CXCL1/G-CSF expression in response to acute aortic dissection triggers local neutrophil recruitment and activation leading to aortic rupture. Circ Res. 116:612–623. 2015. View Article : Google Scholar : PubMed/NCBI
37	Tanios F, Pelisek J, Lutz B, Reutersberg B, Matevossian E, Schwamborn K, Hösel V, Eckstein HH and Reeps C: CXCR4: A potential marker for inflammatory activity in abdominal aortic aneurysm wall. Eur J Vasc Endovasc Surg. 50:745–753. 2015. View Article : Google Scholar : PubMed/NCBI
38	Michineau S, Franck G, Wagner-Ballon O, Dai J, Allaire E and Gervais M: Chemokine (C-X-C motif) receptor 4 blockade by AMD3100 inhibits experimental abdominal aortic aneurysm expansion through anti-inflammatory effects. Arterioscler Thromb Vasc Biol. 34:1747–1755. 2014. View Article : Google Scholar : PubMed/NCBI
39	Ramos-Mozo P, Rodriguez C, Pastor-Vargas C, Blanco-Colio LM, Martinez-Gonzalez J, Meilhac O, Michel JB, de Ceniga Vega M, Egido J and Martin-Ventura JL: Plasma profiling by a protein array approach identifies IGFBP-1 as a novel biomarker of abdominal aortic aneurysm. Atherosclerosis. 221:544–550. 2012. View Article : Google Scholar : PubMed/NCBI
40	Wang J, Razuvaev A, Folkersen L, Hedin E, Roy J, Brismar K and Hedin U: The expression of IGFs and IGF binding proteins in human carotid atherosclerosis, and the possible role of IGF binding protein-1 in the regulation of smooth muscle cell proliferation. Atherosclerosis. 220:102–109. 2012. View Article : Google Scholar : PubMed/NCBI
41	Giancotti FG and Ruoslahti E: Integrin signaling. Science. 285:1028–1032. 1999. View Article : Google Scholar : PubMed/NCBI