Gene expression profiles of HTR8-S/Vneo cells after changes in ABCA1 expression
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ABCA1 is expressed in placental trophoblasts, such that when the expression level of ABCA1 changes, the function of trophoblasts dramatically changes. However, the mechanism by which ABCA1 affects the function of trophoblast cells remains unclear. Here, we used biochemical and transcriptomic to uncover the potential mechanism of the effect of ABCA1 on trophoblast function. HTR8/SVneo cells were either treated with the agonist T0901317 or transfected with siRNA to regulate ABCA1 expression levels. A human gene expression microarray was used to analyze the expression spectrum of ABCA1. Microarray results were confirmed by Western blotting and RT-PCR. Immunofluorescence allowed detection of the cellular localization of ABCA1, CCL8, CXCL10, CXCL11, and S1PR1 in HTR8/SVneo cells. Co-immunoprecipitation was used to test interactions among these proteins. Concomitant with an increase in ABCA1 expression, S1PR1 expression increased, whereas expression of CCL8, CXCL10, and CXCL11 decreased significantly; opposite effects were observed with a decrease in ABCA1 expression. Thus, changes in ABCA1 expression may lead to changes in downstream gene expression. Whereas the interaction between ABCA1 and S1PR1 was direct, interactions among ABCA1 and CCL8, CXCL10, and CXCL11 were indirect. We propose that, in conjunction with S1PR1, ABCA1 regulates expression levels of CCL8, CXCL10, and CXCL11; this may lead to changes in the immune function of trophoblastic cells. Thus, we suspect that the effect of ABCA1 on trophoblast function may involve many biological processes, molecular function changes, and the activation of multiple signaling pathways.
KeywordsABCA1 Gene expression profile Trophoblast Placenta HTR8-S/Vneo cell
This study was funded by the National Natural Science Foundation of China (no. 81471476). The funding bore the cost of the laboratory reagents and antibodies. We thank Prof. Wang H.M. and the laboratory at the Institute of Zoology, Chinese Academy of Sciences for providing the HTR8/SVneo cells. We also thank Chen Wei (Molecular Medicine Section, Department of experimental center, Beijing Friendship Hospital, Beijing, China) for technical help, as well as Wendy Ran and Ryan Chastain-Gross, Ph.D., from Liwen Bianji, Edanz Group China (www.liwenbianji.cn/ac), for editing the English text of a draft of this manuscript.
L.L. designed the project, analyzed the data, and wrote and edited the manuscript. C.X.H and X.C.M designed the project, collected tissues, performed all the experiments, analyzed the data, and wrote and edited the manuscript. L.Y. designed the project, assisted in data analysis, and edited the manuscript. W.X.J., Q.Z.W., and C.X. collected tissues and assisted in some of the experiments. All authors gave their final approval of the submitted version.
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Conflict of interest
The authors declare that they have no conflict of interest.
This article does not contain any studies with human participants performed by any of the authors. This article does not contain any studies with animals performed by any of the authors.
For this type of study, formal consent is not required.
- Baergen RN (2005) Manual of Benirschke and Kaufmann’s. Springer, New YorkGoogle Scholar
- Bodzioch M, Orsó E, Klucken J, Langmann T, Böttcher A, Diederich W, Drobnik W, Barlage S, Büchler C, Porsch-Ozcürümez M, Kaminski WE, Hahmann HW, Oette K, Rothe G, Aslanidis C, Lackner KJ, Schmitz G (1999) The gene encoding ATP-binding cassette transporter 1 is mutated in tangier disease. Nat Genet 22:347–351CrossRefGoogle Scholar
- Christiansen-Weber TA, Voland JR, Wu Y, Ngo K, Roland BL, Nguyen S, Peterson PA, Fung-Leung WP (2000) Functional loss of ABCA1 in mice causes severe placental malformation, aberrant lipid distribution, and kidney glomerulonephritis as well as high-density lipoprotein cholesterol deficiency. Am J Pathol 157:1017–1029CrossRefGoogle Scholar
- Marcil M, Brooks-Wilson A, Clee SM, Roomp K, Zhang LH, Yu L, Collins JA, van Dam M, Molhuizen HO, Loubster O, Ouellette BF, Sensen CW, Fichter K, Mott S, Denis M, Boucher B, Pimstone S, Genest J, Kastelein JJ, Hayden MR (1999) Mutations in the ABC1 gene in familial HDL deficiency with defective cholesterol efflux. Lancet 354:1341–1346CrossRefGoogle Scholar
- Remaley AT, Rust S, Rosier M, Knapper C, Naudin L, Broccardo C, Peterson KM, Koch C, Arnould I, Prades C, Duverger N, Funke H, Assman G, Dinger M, Dean M, Chimini G, Santamarina-Fojo S, Fredrickson DS, Denefle P, Brewer HB (1999) Human ATP-binding cassette transporter 1 (ABC1): genomic organization and identification of the genetic defect in the original tangier disease kindred. Proc Natl Acad Sci U S A 96:12685–12690CrossRefGoogle Scholar