NANOG improves type I collagen expression in human fetal scleral fibroblasts

Authors

  • Xuyan Li 1. Key Laboratory of Animal Cellular and Genetic Engineering of Heilongjiang Province, Northeast Agricultural University, Harbin, 150030; 2. College of Life Science and Agriculture Forestry, Qiqihar University, Qiqihar, 161006
  • Tianfei Yu 1. Key Laboratory of Animal Cellular and Genetic Engineering of Heilongjiang Province, Northeast Agricultural University, Harbin, 150030; 2. College of Life Science and Agriculture Forestry, Qiqihar University, Qiqihar, 161006
  • Ming Li College of Life Science and Agriculture Forestry, Qiqihar University, Qiqihar, 161006
  • Youqi Wang College of Life Science and Agriculture Forestry, Qiqihar University, Qiqihar, 161006
  • Bo Meng College of Life Science and Agriculture Forestry, Qiqihar University, Qiqihar, 161006
  • Yanshuang Mu Key Laboratory of Animal Cellular and Genetic Engineering of Heilongjiang Province, Northeast Agricultural University, Harbin, 150030

Keywords:

NANOG, human fetal scleral fibroblasts, myopia, collagen

Abstract

Paper description:

  • Human fetal scleral fibroblasts (HFSFs) are components of the sclera that are involved in eye growth regulation and myopia formation. Nanog homeobox (NANOG) is a key transcription factor essential for the pluripotent and self-renewing phenotypes of embryonic stem cells.
  • NANOG overexpression in HFSFs improves type I collagen expression and increases proliferation rates of HFSFs. The increase in the number of HFSFs and type I collagen may delay sclera remodeling.
  • Our findings contribute to the development of more effictive theoretical support for myopia treatment.

Abstract: Human fetal scleral fibroblasts (HFSFs) are components of the sclera and play important roles in its structure and function. In myopia, scleral remodeling reduces collagen fibers and the sclera begins to thin. NANOG is a key transcription factor essential for pluripotent and self-renewing phenotypes of undifferentiated embryonic stem cells. To determine whether NANOG improves human fetal scleral fibroblast quality and the underlying mechanisms in these cells, we established stable NANOG-overexpressing HFSFs. We studied type I collagen (COL1A 1) and Rho-associated coiled-coil protein kinase 1 (ROCK1) expression in transfected cells. We also investigated POU5F1, SOX2, KLF4, MYC and SALL4 expression in NANOG stably-overexpressed fibroblasts. Our data show that NANOG expression increased proliferation rates in fibroblasts. When compared to controls, expression of COL1A 1 in transfected fibroblasts was increased and the expression of ROCK1 was decreased. Similarly, the expression of POU5F1, SOX2 and KLF4 was downregulated, the expression of MYC was upregulated and there was no significant change in the expression of SALL4 in transfected fibroblasts. Our results suggest that in fibroblasts, NANOG regulates ROCK1 expression and improves COL1A 1 expression to delay scleral remodeling.

https://doi.org/10.2298/ABS180711048L

Received: July 11, 2018; Revised: September 15, 2018; Accepted: October 11, 2018; Published online: October 23, 2018

How to cite this article: Li X, Yu T, Li M, Wang Y, Meng B, Mu Y. NANOG improves type I collagen expression in human fetal scleral fibroblasts. Arch Biol Sci. 2019;71(1):63-70.

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References

Holden B, Sankaridurg P, Smith E, Aller T, Jong M, He M. Myopia, an underrated global challenge to vision: where the current data takes us on myopia control. Eye (Lond). 2014;28:142-6.

Watson PG, Young RD. Scleral structure, organisation and disease. A review. Exp Eye Res. 2004;78:609-23.

McBrien NA, Cornell LM, Gentle A. Structural and ultrastructural changes to the sclera in a mammalian model of high myopia. Invest Ophthalmol Vis Sci. 2001;42:2179-87.

Gentle A, Liu Y, Martin JE, Conti GL, McBrien NA. Collagen gene expression and the altered accumulation of scleral collagen during the development of high myopia. J Biol Chem. 2003;278:16587-94.

McBrien NA, Gentle A. Role of the sclera in the development and pathological complications of myopia. Prog Retin Eye Res. 2003;22:307-38.

Hu S, Cui D, Yang X, Hu J, Wan W, Zeng J. The crucial role of collagen-binding integrins in maintaining the mechanical properties of human scleral fibroblasts-seeded collagen matrix. Mol Vis. 2011;17:1334-42.

Rada JA, Nickla DL, Troilo D. Decreased proteoglycan synthesis associated with form deprivation myopia in mature primate eyes. Invest Ophthalmol Vis Sci. 2000;41:2050-8.

Rada JA, Johnson JM, Achen VR, Rada KG. Inhibition of scleral proteoglycan synthesis blocks deprivation-induced axial elongation in chicks. Exp Eye Res. 2002;74:205-15.

Cui W, Bryant MR, Sweet PM, McDonnell PJ. Changes in gene expression in response to mechanical strain in human scleral fibroblasts. Exp Eye Res. 2004;78:275-84.

Silva J, Chambers I, Pollard S, Smith A. Nanog promotes transfer of pluripotency after cell fusion. Nature. 2006;441:997-1001.

Silva J, Nichols J, Theunissen TW, Guo G, van Oosten AL, Barrandon O, Wray J, Yamanaka S, Chambers I, Smith A. Nanog is the gateway to the pluripotent ground state. Cell. 2009;138: 722-37.

Chambers I, Colby D, Robertson M, Nichols J, Lee S, Tweedie S, Smith A. Functional expression cloning of Nanog, a pluripotency sustaining factor in embryonic stem cells. Cell. 2003;113:643-55.

Mitsui K, Tokuzawa Y, Itoh H, Segawa K, Murakami M, Takahashi K, Maruyama M, Maeda M, Yamanaka S. The homeoprotein Nanog is required for maintenance of pluripotency in mouse epiblast and ES cells. Cell. 2003;113:631-42.

Miyanari Y, Torres-Padilla ME. Control of ground-state pluripotency by allelic regulation of Nanog. Nature. 2012;483:470-3.

Yu J, Vodyanik MA, Smuga-Otto K, Antosiewicz-Bourget J, Frane JL, Tian S, Nie J, Jonsdottir GA, Ruotti V, Stewart R, Slukvin II, Thomson JA. Induced pluripotent stem cell lines derived from human somatic cells. Science. 2007;318:1917-20.

Choi KD, Yu J, Smuga-Otto K, Salvagiotto G, Rehrauer W, Vodyanik M, Thomson J, Slukvin I. Hematopoietic and endothelial differentiation of human induced pluripotent stem cells. Stem Cells. 2009;27:559-67.

Hanna J, Saha K, Pando B, van Zon J, Lengner CJ, Creyghton MP, van Oudenaarden A, Jaenisch R. Direct cell reprogramming is a stochastic process amenable to acceleration. Nature. 2009;462:595-601.

Takahashi K , Yamanaka S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell. 2006;126:663-76.

Okita K, Ichisaka T, Yamanaka S. Generation of germline-competent induced pluripotent stem cells. Nature. 2007;448:313-7.

Zhang J, Wang X, Chen B, Suo G, Zhao Y, Duan Z, Dai J. Expression of Nanog gene promotes NIH3T3 cell proliferation. Biochem Biophys Res Commun. 2005;338:1098-102.

Piestun D, Kochupurakkal BS, Jacob-Hirsch J, Zeligson S, Koudritsky M, Domany E, Amariglio N, Rechavi G, Givol D. Nanog transforms NIH3T3 cells and targets cell-type restricted genes. Biochem Biophys Res Commun. 2006;343:279-85.

Huo L, Cui D, Yang X, Gao Z, Trier K, Zeng J. All-trans retinoic acid modulates mitogen-activated protein kinase pathway activation in human scleral fibroblasts through retinoic acid receptor beta. Mol Vis. 2013;19:1795-803.

Cui D, Trier K, Chen X, Zeng J, Yang X, Hu J, Ge J. Distribution of adenosine receptors in human sclera fibroblasts. Mol Vis. 2008;14:523-9.

Boyer LA, Lee TI, Cole MF, Johnstone SE, Levine SS, Zucker JP, Guenther MG, Kumar RM, Murray HL, Jenner RG, Gifford DK, Melton DA, Jaenisch R, Young RA. Core transcriptional regulatory circuitry in human embryonic stem cells. Cell. 2005;122:947-56.

Do HJ, Lim HY, Kim JH, Song H, Chung HM, Kim JH. An intact homeobox domain is required for complete nuclear localization of human Nanog. Biochem Biophys Res Commun. 2007;353:770-5.

Curtin BJ, Teng CC. Scleral changes in pathological myopia. Trans Am Acad Ophthalmol Otolaryngol. 1958;62:777-88;discussion 88-90.

Curtin BJ, Iwamoto T, Renaldo DP. Normal and staphylomatous sclera of high myopia. An electron microscopic study. Arch Ophthalmol. 1979;97:912-5.

Seyhan N, Canseven AG. In vivo effects of ELF MFs on collagen synthesis, free radical processes, natural antioxidant system, respiratory burst system, immune system activities, and electrolytes in the skin, plasma, spleen, lung, kidney, and brain tissues. Electromagn Biol Med. 2006;25:291-305.

Nakajima H, Kishi T, Tsuchiya Y, Yamada H, Tajima S. Exposure of fibroblasts derived from keloid patients to low-energy electromagnetic fields: preferential inhibition of cell proliferation, collagen synthesis, and transforming growth factor beta expression in keloid fibroblasts in vitro. Ann Plast Surg. 1997;39:536-41.

Zhang X, Neganova I, Przyborski S, Yang C, Cooke M, Atkinson SP, Anyfantis G, Fenyk S, Keith WN, Hoare SF, Hughes O, Strachan T, Stojkovic M, Hinds PW, Armstrong L, Lako M. A role for NANOG in G1 to S transition in human embryonic stem cells through direct binding of CDK6 and CDC25A. J Cell Biol. 2009;184:67-82.

Jeter CR, Liu B, Liu X, Chen X, Liu C, Calhoun-Davis T, Repass J, Zaehres H, Shen JJ, Tang DG. NANOG promotes cancer stem cell characteristics and prostate cancer resistance to androgen deprivation. Oncogene. 2011;30:3833-45.

Han J, Zhang F, Yu M, Zhao P, Ji W, Zhang H, Wu B, Wang Y, Niu R. RNA interference-mediated silencing of NANOG reduces cell proliferation and induces G0/G1 cell cycle arrest in breast cancer cells. Cancer Lett. 2012;321:80-8.

Jobling AI, Gentle A, Metlapally R, McGowan BJ, McBrien NA. Regulation of scleral cell contraction by transforming growth factor-beta and stress: competing roles in myopic eye growth. J Biol Chem. 2009;284:2072-9.

Wessel H, Anderson S, Fite D, Halvas E, Hempel J, SundarRaj N. Type XII collagen contributes to diversities in human corneal and limbal extracellular matrices. Invest Ophthalmol Vis Sci. 1997;38:2408-22.

Metlapally R, Li YJ, Tran-Viet KN, Abbott D, Czaja GR, Malecaze F, Calvas P, Mackey D, Rosenberg T, Paget S, Zayats T, Owen MJ, Guggenheim JA, Young TL. COL1A1 and COL2A1 genes and myopia susceptibility: evidence of association and suggestive linkage to the COL2A1 locus. Invest Ophthalmol Vis Sci. 2009;50:4080-6.

Nakanishi H, Yamada R, Gotoh N, Hayashi H, Yamashiro K, Shimada N, Ohno-Matsui K, Mochizuki M, Saito M, Iida T, Matsuo K, Tajima K, Yoshimura N, Matsuda F. A genome-wide association analysis identified a novel susceptible locus for pathological myopia at 11q24.1. PLoS Genet. 2009;5:e1000660.

Nakayamada S, Kurose H, Saito K, Mogami A, Tanaka Y. Small GTP-binding protein Rho-mediated signaling promotes proliferation of rheumatoid synovial fibroblasts. Arthritis Res Ther. 2005;7:R476-84.

Ridley AJ. Rho family proteins: coordinating cell responses. Trends Cell Biol. 2001;11:471-7.

Zhu J, Nguyen D, Ouyang H, Zhang XH, Chen XM, Zhang K. Inhibition of RhoA/Rho-kinase pathway suppresses the expression of extracellular matrix induced by CTGF or TGF-beta in ARPE-19. Int J Ophthalmol. 2013;6:8-14.

Huang CE, Hu FW, Yu CH, Tsai LL, Lee TH, Chou MY, Yu CC. Concurrent expression of Oct4 and Nanog maintains mesenchymal stem-like property of human dental pulp cells. Int J Mol Sci. 2014;15:18623-39.

Chan KK, Zhang J, Chia NY, Chan YS, Sim HS, Tan KS, Oh SK, Ng HH, Choo AB. KLF4 and PBX1 directly regulate NANOG expression in human embryonic stem cells. Stem Cells. 2009;27:2114-25.

Wu Q, Chen X, Zhang J, Loh YH, Low TY, Zhang W, Zhang W, Sze SK, Lim B, Ng HH. Sall4 interacts with Nanog and co-occupies Nanog genomic sites in embryonic stem cells. J Biol Chem. 2006;281:24090-4.

Bretones G, Delgado MD, Leon J. Myc and cell cycle control. Biochim Biophys Acta. 2015;1849:506-16.

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Published

2019-04-02

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1.
Li X, Yu T, Li M, Wang Y, Meng B, Mu Y. NANOG improves type I collagen expression in human fetal scleral fibroblasts. Arch Biol Sci [Internet]. 2019Apr.2 [cited 2024Apr.16];71(1):63-70. Available from: https://www.serbiosoc.org.rs/arch/index.php/abs/article/view/3187

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Vol. 71 No. 1 (2019)

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