Regulation of dual specificity phosphatases by fibroblast growth factor signaling pathways in bovine granulosa cells

in Reproduction
Authors:
Lauriane Relav Centre de Recherche en Reproduction et Fertilité, Faculté de Médecine Vétérinaire, Université de Montréal, St-Hyacinthe, Quebec, Canada

Search for other papers by Lauriane Relav in
Current site
Google Scholar
PubMed Close
and
Christopher A Price Centre de Recherche en Reproduction et Fertilité, Faculté de Médecine Vétérinaire, Université de Montréal, St-Hyacinthe, Quebec, Canada

Search for other papers by Christopher A Price in
Current site
Google Scholar
PubMed Close

Correspondence should be addressed to C A Price; Email: christopher.price@umontreal.ca

†(L Relav is now at Institut de Pharmacologie Moléculaire et Cellulaire, CNRS UMR7275, Sophia Antipolis, Valbonne, France)

DOI:
https://doi.org/10.1530/REP-21-0270
Volume/Issue:
Volume 162: Issue 5
Page Range:
367–374
Article Type:
Research Article
Online Publication Date:
05 Oct 2021
Copyright:
© Society for Reproduction and Fertility 2021
Restricted access
Rent on DeepDyve

Sign up for journal news

Controling the duration and amplitude of mitogen-activated protein kinase (MAPK) signaling is an important element in deciding cell fate. One group of intracellular negative regulators of MAPK activity is a subfamily of the dual specificity phosphatase (DUSP) superfamily, of which up to 16 members have been described in the ovarian granulosa cells. Growth factors stimulate proliferation of granulosa cells through MAPK, protein kinase C (PKC), and AKT pathways, although it is not known which pathways control DUSP expression in these cells. The aim of the present study was to identify which pathways were involved in the regulation of DUSP expression using a well-established serum-free culture system for bovine granulosa cells. Stimulation of cells with FGF2 increased DUSP1, DUSP5, and DUSP6 mRNA abundance in a time- and dose-dependent manner, and increased DUSP5 and DUSP6 protein accumulation. None of the other eleven DUSP measured were regulated by FGF2. Pharmacological inhibition of MAPK3/1 signaling decreased FGF2-stimulated DUSP1, DUSP5, and DUSP6 mRNA levels (P  < 0.05), whereas inhibition of PKC did not affect the expression of these three DUSPs. Abundance of FGF2-dependent DUSP6 mRNA was reduced by inhibition of phospholipase C (PLC) or by chelating calcium, but DUSP5 mRNA abundance was not affected. Abundance of basal DUSP1 and DUSP6, but not DUSP5 mRNA was increased by the addition of the calcium ionophore A23187. We conclude that FGF2 stimulation of DUSP5 abundance requires MAPK3/1 whereas DUSP6 mRNA accumulation is dependent on calcium signaling as well as MAPK3/1 activation, suggesting complex regulation of physiologically important DUSPs in the follicle.

Reproduction is committed to supporting researchers in demonstrating the impact of their articles published in the journal.

The two types of article metrics we measure are (i) more traditional full-text views and pdf downloads, and (ii) Altmetric data, which shows the wider impact of articles in a range of non-traditional sources, such as social media.

More information is on the Reasons to publish page.

Sept 2018 onwards Past Year Past 30 Days
Full Text Views 1219 121 1
PDF Downloads 297 31 3

 

  • Collapse
  • Expand
Print ISSN:
1470-1626
Online ISSN:
1741-7899

  • Cabrita MA & Christofori G 2008 Sprouty proteins, masterminds of receptor tyrosine kinase signaling. Angiogenesis 11 53–62. (https://doi.org/10.1007/s10456-008-9089-1)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Camps M, Nichols A & Arkinstall S 2000 Dual specificity phosphatases: a gene family for control of MAP kinase function. FASEB Journal 14 6–16. (https://doi.org/10.1096/fasebj.14.1.6)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Chaves RN, de Matos MH, Buratini J & de Figueiredo JR 2012 The fibroblast growth factor family: involvement in the regulation of folliculogenesis. Reproduction, Fertility, and Development 24 905–915. (https://doi.org/10.1071/RD11318)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Damon DH, Lange DL & Hattler BG 1997 In vitro and in vivo vascular actions of basic fibroblast growth factor (bFGF) in normotensive and spontaneously hypertensive rats. Journal of Cardiovascular Pharmacology 30 278–284. (https://doi.org/10.1097/00005344-199709000-00002)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Donaubauer EM, Law NC & Hunzicker-Dunn ME 2016 Follicle-stimulating hormone (FSH)-dependent regulation of extracellular regulated kinase (ERK) phosphorylation by the mitogen-activated protein (MAP) kinase phosphatase MKP3. Journal of Biological Chemistry 291 19701–19712. (https://doi.org/10.1074/jbc.M116.733972)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Durham PL & Russo AF 2000 Differential regulation of mitogen-activated protein kinase-responsive genes by the duration of a calcium signal. Molecular Endocrinology 14 1570–1582. (https://doi.org/10.1210/mend.14.10.0529)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Ebisuya M, Kondoh K & Nishida E 2005 The duration, magnitude and compartmentalization of ERK MAP kinase activity: mechanisms for providing signaling specificity. Journal of Cell Science 118 2997–3002. (https://doi.org/10.1242/jcs.02505)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Ehrengruber MU, Muhlebach SG, Söhrman S, Leutenegger CM, Lester HA & Davidson N 2000 Modulation of early growth response (EGR) transcription factor-dependent gene expression by using recombinant adenovirus. Gene 258 63–69. (https://doi.org/10.1016/s0378-1119(0000445-5)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Ekerot M, Stavridis MP, Delavaine L, Mitchell MP, Staples C, Owens DM, Keenan ID, Dickinson RJ, Storey KG & Keyse SM 2008 Negative-feedback regulation of FGF signalling by DUSP6/MKP-3 is driven by ERK1/2 and mediated by Ets factor binding to a conserved site within the DUSP6/MKP-3 gene promoter. Biochemical Journal 412 287–298. (https://doi.org/10.1042/BJ20071512)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Gilmore PM, Quinn JE, Mullan PB, Andrews HN, McCabe N, Carty M, Kennedy RD & Harkin DP 2003 Role played by BRCA1 in regulating the cellular response to stress. Biochemical Society Transactions 31 257–262. (https://doi.org/10.1042/bst0310257)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Gutiérrez CG, Campbell BK & Webb R 1997 Development of a long-term bovine granulosa cell culture system: induction and maintenance of estradiol production, response to follicle-stimulating hormone, and morphological characteristics. Biology of Reproduction 56 608–616. (https://doi.org/10.1095/biolreprod56.3.608)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Han P, Guerrero-Netro H, Estienne A, Cao B & Price CA 2017 Regulation and action of early growth response 1 in bovine granulosa cells. Reproduction 154 547–557. (https://doi.org/10.1530/REP-17-0243)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Han P, Relav L & Price CA 2020 Regulation of the early growth response-1 binding protein NAB2 in bovine granulosa cells and effect on connective tissue growth factor expression. Molecular and Cellular Endocrinology 518 111041. (https://doi.org/10.1016/j.mce.2020.111041)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Herndon MK, Law NC, Donaubauer EM, Kyriss B & Hunzicker-Dunn M 2016 Forkhead box O member FOXO1 regulates the majority of follicle-stimulating hormone responsive genes in ovarian granulosa cells. Molecular and Cellular Endocrinology 434 116–126. (https://doi.org/10.1016/j.mce.2016.06.020)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Huang M, Li X, Jia S, Liu S, Fu L, Jiang X & Yang M 2021 Bisphenol AF induces apoptosis via estrogen receptor beta (ERβ) and ROS-ASK1-JNK MAPK pathway in human granulosa cell line KGN. Environmental Pollution 270 116051. (https://doi.org/10.1016/j.envpol.2020.116051)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Irving-Rodgers HF, van Wezel IL, Mussard ML, Kinder JE & Rodgers RJ 2001 Atresia revisited: two basic patterns of atresia of bovine antral follicles. Reproduction 761–775.(https://doi.org/10.1530/rep.0.1220761)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Jiang ZL, Ripamonte P, Buratini J, Portela VM & Price CA 2011 Fibroblast growth factor-2 regulation of Sprouty and NR4A genes in bovine ovarian granulosa cells. Journal of Cellular Physiology 226 1820–1827. (https://doi.org/10.1002/jcp.22509)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Jiang Z, Guerrero-Netro HM, Juengel JL & Price CA 2013 Divergence of intracellular signaling pathways and early response genes of two closely related fibroblast growth factors, FGF8 and FGF18, in bovine ovarian granulosa cells. Molecular and Cellular Endocrinology 375 97–105. (https://doi.org/10.1016/j.mce.2013.05.017)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Khan DR, Guillemette C, Sirard MA & Richard FJ 2015 Characterization of FSH signalling networks in bovine cumulus cells: a perspective on oocyte competence acquisition. Molecular Human Reproduction 21 688–701. (https://doi.org/10.1093/molehr/gav032)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Kidger AM & Keyse SM 2016 The regulation of oncogenic Ras/ERK signalling by dual-specificity mitogen activated protein kinase phosphatases (MKPs). Seminars in Cell and Developmental Biology 50 125–132. (https://doi.org/10.1016/j.semcdb.2016.01.009)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Kubosaki A, Tomaru Y, Tagami M, Arner E, Miura H, Suzuki T, Suzuki M, Suzuki H & Hayashizaki Y 2009 Genome-wide investigation of in vivo EGR-1 binding sites in monocytic differentiation. Genome Biology 10 R41. (https://doi.org/10.1186/gb-2009-10-4-r41)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Kucharska A, Rushworth LK, Staples C, Morrice NA & Keyse SM 2009 Regulation of the inducible nuclear dual-specificity phosphatase DUSP5 by ERK MAPK. Cellular Signalling 21 1794–1805. (https://doi.org/10.1016/j.cellsig.2009.07.015)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Liu S, Shen M, Li C, Wei Y, Meng X, Li R, Cao Y, Wu W & Liu H 2019 PKCδ contributes to oxidative stress-induced apoptosis in porcine ovarian granulosa cells via activating JNK. Theriogenology 131 89–95. (https://doi.org/10.1016/j.theriogenology.2019.03.023)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Liu Z, Li C, Wu G, Li W, Zhang X, Zhou J, Zhang L, Tao J, Shen M & Liu H 2020 Involvement of JNK/FOXO1 pathway in apoptosis induced by severe hypoxia in porcine granulosa cells. Theriogenology 154 120–127. (https://doi.org/10.1016/j.theriogenology.2020.05.019)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Lo LW, Cheng JJ, Chiu JJ, Wung BS, Liu YC & Wang DL 2001 Endothelial exposure to hypoxia induces Egr-1 expression involving PKCα-mediated Ras/Raf-1/ERK1/2 pathway. Journal of Cellular Physiology 188 304–312. (https://doi.org/10.1002/jcp.1124)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Marshall CJ 1995 Specificity of receptor tyrosine kinase signaling: transient versus sustained extracellular signal-regulated kinase activation. Cell 80 179–185. (https://doi.org/10.1016/0092-8674(9590401-8)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Mason JM, Morrison DJ, Basson MA & Licht JD 2006 Sprouty proteins: multifaceted negative-feedback regulators of receptor tyrosine kinase signaling. Trends in Cell Biology 16 45–54. (https://doi.org/10.1016/j.tcb.2005.11.004)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Matsuda F, Inoue N, Manabe N & Ohkura S 2012 Follicular growth and atresia in mammalian ovaries: regulation by survival and death of granulosa cells. Journal of Reproduction and Development 58 44–50. (https://doi.org/10.1262/jrd.2011-012)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Miyoshi T, Otsuka F, Yamashita M, Inagaki K, Nakamura E, Tsukamoto N, Takeda M, Suzuki J & Makino H 2010 Functional relationship between fibroblast growth factor-8 and bone morphogenetic proteins in regulating steroidogenesis by rat granulosa cells. Molecular and Cellular Endocrinology 325 84–92. (https://doi.org/10.1016/j.mce.2010.04.012)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Patterson KI, Brummer T, O’Brien PM & Daly RJ 2009 Dual-specificity phosphatases: critical regulators with diverse cellular targets. Biochemical Journal 418 475–489. (https://doi.org/10.1042/bj20082234)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Peluso JJ, Pappalardo A & Fernandez G 2001 Basic fibroblast growth factor maintains calcium homeostasis and granulosa cell viability by stimulating calcium efflux via a PKCδ-dependent pathway. Endocrinology 142 4203–4211. (https://doi.org/10.1210/endo.142.10.8460)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Pfaffl MW 2001 A new mathematical model for relative quantification in real-time RT-PCR. Nucleic Acids Research 29 e45. (https://doi.org/10.1093/nar/29.9.e45)

  • Price CA & Estienne A 2018 The life and death of the dominant follicle. Animal Reproduction 15 680–690. (https://doi.org/10.21451/1984-3143-AR2018-0030)

  • Relav L, Estienne A & Price CA 2021 Dual-specificity phosphatase 6 (DUSP6) mRNA and protein abundance is regulated by fibroblast growth factor 2 in sheep granulosa cells and inhibits c-Jun N-terminal kinase (MAPK8) phosphorylation. Molecular and Cellular Endocrinology 531 111297. (https://doi.org/10.1016/j.mce.2021.111297)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Scimeca JC, Servant MJ, Dyer JO & Meloche S 1997 Essential role of calcium in the regulation of MAP kinase phosphatase-1 expression. Oncogene 15 717–725. (https://doi.org/10.1038/sj.onc.1201231)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Sen A, Lv L, Bello N, Ireland JJ & Smith GW 2008 Cocaine- and amphetamine-regulated transcript accelerates termination of follicle-stimulating hormone-induced extracellularly regulated kinase 1/2 and Akt activation by regulating the expression and degradation of specific mitogen-activated protein kinase phosphatases in bovine granulosa cells. Molecular Endocrinology 22 2655–2676. (https://doi.org/10.1210/me.2008-0077)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Silva JM & Price CA 2000 Effect of follicle-stimulating hormone on steroid secretion and messenger ribonucleic acids encoding cytochromes P450 aromatase and cholesterol side-chain cleavage in bovine granulosa cells in vitro. Biology of Reproduction 62 186–191. (https://doi.org/10.1095/biolreprod62.1.186)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Weng Q, Liu Z, Li B, Liu K, Wu W & Liu H 2016 Oxidative stress induces mouse follicular granulosa cells apoptosis via JNK/FoxO1 pathway. PLoS ONE 11 e0167869. (https://doi.org/10.1371/journal.pone.0167869)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Woods DC & Johnson AL 2006 Phosphatase activation by epidermal growth factor family ligands regulates extracellular regulated kinase signaling in undifferentiated hen granulosa cells. Endocrinology 147 4931–4940. (https://doi.org/10.1210/en.2006-0194)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Yang MY & Rajamahendran R 2000 Involvement of apoptosis in the atresia of nonovulatory dominant follicle during the bovine estrous cycle. Biology of Reproduction 63 1313–1321. (https://doi.org/10.1095/biolreprod63.5.1313)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Zhang Z, Kobayashi S, Borczuk AC, Leidner RS, Laframboise T, Levine AD & Halmos B 2010 Dual specificity phosphatase 6 (DUSP6) is an ETS-regulated negative feedback mediator of oncogenic ERK signaling in lung cancer cells. Carcinogenesis 31 577–586. (https://doi.org/10.1093/carcin/bgq020)

    • PubMed
    • Search Google Scholar
    • Export Citation