Skip to main content
SpringerLink
Log in

Cell-type-specific expression of murine multifunctional galectin-3 and its association with follicular atresia/luteolysis in contrast to pro-apoptotic galectins-1 and -7

  • Original Paper
  • Published:
Histochemistry and Cell Biology Aims and scope Submit manuscript

Abstract

Galectin-3 is a multifunctional protein with modular design. A distinct expression profile was determined in various murine organs when set into relation to homodimeric galectins-1 and -7. Fittingly, the signature of putative transcription-factor-binding sites in the promoter region of the galectin-3 gene affords a toolbox for a complex combinatorial regulation, distinct from the respective sequence stretches in galectins-1 and -7. A striking example for cell-type specificity was the ovary, where these two lectins were confined to the surface epithelium. Immunohistochemically, galectin-3 was found in macrophages of the cortical interstitium between developing follicles and medullary interstitium, matching the distribution of the F4/80 antigen. With respect to atresia and luteolysis strong signals in granulosa cells of atretic preantral but not antral follicles and increasing positivity in corpora lutea upon regression coincided with DNA fragmentation. Labeled galectin-3 revealed lactose-inhibitable binding to granulosa cells. Also, slender processes of vital granulosa cells which extended into the zona pellucida were positive. This study demonstrates cell-type specificity and cycle-associated regulation for galectin-3 with increased presence in atretic preantral follicles and in late stages of luteolysis.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  • Ahmad N, Gabius HJ, André S, Kaltner H, Sabesan S, Roy R, Liu B, Macaluso F, Brewer CF (2004) Galectin-3 precipitates as a pentamer with synthetic multivalent carbohydrates and forms heterogeneous cross-linked complexes. J Biol Chem 279:10841–10847

    Article  PubMed  CAS  Google Scholar 

  • André S, Liu B, Gabius HJ, Roy R (2003) First demonstration of differential inhibition of lectin binding by synthetic tri- and tetravalent glycoclusters from cross-coupling of rigidified 2-propynyl lactoside. Org Biomol Chem 1:3909–3916

    Article  PubMed  Google Scholar 

  • André S, Kaltner H, Furuike T, Nishimura SI, Gabius HJ (2004) Persubstituted cyclodextrin-based glycoclusters as inhibitors of protein-carbohydrate recognition using purified plant and mammalian lectins and wild-type and lectin-gene-transfected tumor cells as targets. Bioconjug Chem 15:87–98

    Article  PubMed  Google Scholar 

  • André S, Kaltner H, Lensch M, Russwurm R, Siebert HC, Fallsehr C, Tajkhorshid E, Heck AJR, von Knebel-Döberitz M, Gabius HJ, Kopitz J (2005) Determination of structural and functional overlap/divergence of five proto-type galectins by analysis of the growth-regulatory interaction with ganglioside GM1 in silico and in vitro on human neuroblastoma cells. Int J Cancer 114:46–57

    Article  PubMed  Google Scholar 

  • André S, Pei Z, Siebert HC, Ramström O, Gabius HJ (2006) Glycosyldisulfides from dynamic combinatorial libraries as O-glycoside mimetics for plant and endogenous lectins: their reactivities in solid-phase and cell assays and conformational analysis by molecular dynamics simulations. Bioorg Med Chem 14:6314–6326

    Article  PubMed  Google Scholar 

  • André S, Sanchez-Ruderisch H, Nakagawa H, Buchholz M, Kopitz J, Forberich P, Kemmner W, Böck C, Deguchi K, Detjen KM, Wiedenmann B, von Knebel-Döberitz M, Gress TM, Nishimura SI, Rosewicz S, Gabius HJ (2007) Tumor suppressor p16INK4a: modulator of glycomic profile and galectin-1 expression to increase susceptibility to carbohydrate-dependent induction of anoikis in pancreatic carcinoma cells. FEBS J 273:3233–3256

    Article  Google Scholar 

  • Arnoys EJ, Wang JL (2007) Dual localization: proteins in extracellular and intracellular compartments. Acta Histochem 109:89–110

    Article  PubMed  CAS  Google Scholar 

  • Aubin JE, Gupta AK, Bhargava U, Turksen K (1996) Expression and regulation of galectin-3 in rat osteoblastic cells. J Cell Physiol 169:468–480

    Article  PubMed  CAS  Google Scholar 

  • Bernerd F, Sarasin A, Magnaldo T (1999) Galectin-7 overexpression is associated with the apoptotic process in UVB-induced sunburn keratinocytes. Proc Natl Acad Sci USA 96:11329–11334

    Article  PubMed  CAS  Google Scholar 

  • Carambula SF, Matikainen T, Lynch MP, Flavell RA, Gonçalves PBD, Tilly JL, Rueda BR (2002) Caspase-3 is a pivotal mediator of apoptosis during regression of the ovarian corpus luteum. Endocrinology 143:1495–1501

    Article  PubMed  CAS  Google Scholar 

  • Choe YS, Shim C, Choi D, Lee CS, Lee KK, Kim K (1997) Expression of galectin-1 mRNA in the mouse uterus is under the control of ovarian steroids during blastocyst implantation. Mol Reprod Dev 48:261–266

    Article  PubMed  CAS  Google Scholar 

  • Choi EJ, Ha CM, Choi J, Kang SS, Choi WS, Park SK, Kim K, Lee BJ (2001) Low-density cDNA array-coupled to PCR differential display identifies new estrogen-responsive genes during the postnatal differentiation of the rat hypothalamus. Mol Brain Res 97:115–128

    Article  PubMed  CAS  Google Scholar 

  • Colnot C, Sidhu SS, Balmain N, Poirier F (2001) Uncoupling of chondrocyte death and vascular invasion in mouse galectin-3 null mutant bones. Dev Biol 229:203–214

    Article  PubMed  CAS  Google Scholar 

  • Davis JS, Rueda BR (2002) The corpus luteum: an ovarian structure with maternal instincts and suicidal tendencies. Front Biosci 7:d1949–d1978

    Article  PubMed  CAS  Google Scholar 

  • Fischer C, Sanchez-Ruderisch H, Welzel M, Wiedenmann B, Sakai T, André S, Gabius HJ, Khachigian L, Detjen KM, Rosewicz S (2005) Galectin-1 interacts with the α5β1 fibronectin receptor to restrict carcinoma cell growth via induction of p21 and p27. J Biol Chem 280:37266–37277

    Article  PubMed  CAS  Google Scholar 

  • Gabius HJ (1997) Animal lectins. Eur J Biochem 243:543–576

    Article  PubMed  CAS  Google Scholar 

  • Gabius HJ (2006) Cell surface glycans: the why and how of their functionality as biochemical signals in lectin-mediated information transfer. Crit Rev Immunol 26:43–79

    PubMed  CAS  Google Scholar 

  • Gabius HJ (ed) (2008) The sugar code. Fundamentals of glycosciences. Wiley/VCH, Weinheim

  • Gabius HJ, Wosgien B, Hendrys M, Bardosi A (1991) Lectin localization in human nerve by biochemically defined lectin-binding glycoproteins, neoglycoprotein and lectin-specific antibody. Histochemistry 95:269–277

    Article  PubMed  CAS  Google Scholar 

  • Gabius HJ, Siebert HC, André S, Jiménez-Barbero J, Rüdiger H (2004) Chemical biology of the sugar code. ChemBioChem 5:740–764

    Google Scholar 

  • Gong HC, Honjo Y, Nangia-Makker P, Hogan V, Mazurak N, Bresalier RS, Raz A (1999) The NH2 terminus of galectin-3 governs cellular compartmentalization and functions in cancer cells. Cancer Res 59:6239–6245

    PubMed  CAS  Google Scholar 

  • Honjo Y, Inohara H, Akahani S, Yoshii T, Takenaka Y, Yoshida JI, Hattori K, Tomiyama Y, Raz A, Kubo T (2000) Expression of cytoplasmic galectin-3 as a prognostic marker in tongue carcinoma. Clin Cancer Res 6:4635–4640

    PubMed  CAS  Google Scholar 

  • Hsu SY, Lai RJM, Finegold M, Hsueh AJW (1996) Targeted overexpression of Bcl-2 in ovaries of transgenic mice leads to decreased follicle apoptosis, enhanced folliculogenesis, and increased germ cell tumorigenesis. Endocrinology 137:4837–4843

    Article  PubMed  CAS  Google Scholar 

  • Jeffery CJ (2003) Multifunctional proteins: examples of gene sharing. Ann Med 35:28–35

    Article  PubMed  CAS  Google Scholar 

  • Kaltner H, Seyrek K, Heck A, Sinowatz F, Gabius HJ (2002) Galectin-1 and galectin-3 in fetal development of bovine respiratory and digestive tracts. Cell Tissue Res 307:35–46

    Article  PubMed  CAS  Google Scholar 

  • Kayser K, Trott J, Böhm G, Huber M, Kaltner H, André S, Gabius HJ (2005) Localized fibrous tumors (LFTs) of the pleura: clinical data, asbestos burden, and syntactic structure analysis applied to newly defined angiogenic/growth-regulatory effectors. Pathol Res Pract 201:791–801

    Article  PubMed  CAS  Google Scholar 

  • Kim H, Lee J, Hyun JW, Park JW, Joo HG, Shin T (2007) Expression and immunohistochemical localization of galectin-3 in various mouse tissues. Cell Biol Int 31:655–662

    Article  PubMed  CAS  Google Scholar 

  • Kopitz J, von Reitzenstein C, André S, Kaltner H, Uhl J, Ehemann V, Cantz M, Gabius HJ (2001) Negative regulation of neuroblastoma cell growth by carbohydrate-dependent surface binding of galectin-1 and functional divergence from galectin-3. J Biol Chem 276:35917–35923

    Article  PubMed  CAS  Google Scholar 

  • Kopitz J, André S, von Reitzenstein C, Versluis K, Kaltner H, Pieters RJ, Wasano K, Kuwabara I, Liu FT, Cantz M, Heck AJR, Gabius HJ (2003) Homodimeric galectin-7 (p53-induced gene 1) is a negative growth regulator for human neuroblastoma cells. Oncogene 22:6277–6288

    Article  PubMed  CAS  Google Scholar 

  • Kübler D, Hung CW, Dam TK, Kopitz J, André S, Kaltner H, Lohr M, Manning JC, He L, Wang H, Middelberg A, Brewer CF, Reed J, Lehmann WD, Gabius HJ (2008) Phosphorylated human galectin-3: facile large-scale preparation of active lectin and detection of structural changes by CD spectroscopy. Biochim Biophys Acta 1780:716–722

    PubMed  Google Scholar 

  • Lensch M, Lohr M, Russwurm R, Vidal M, Kaltner H, André S, Gabius HJ (2006) Unique sequence and expression profiles of rat galectins-5 and -9 as a result of species-specific gene divergence. Int J Biochem Cell Biol 38:1741–1758

    Article  PubMed  CAS  Google Scholar 

  • Liu FT, Patterson RJ, Wang JL (2002) Intracellular functions of galectins. Biochim Biophys Acta 1572:263–273

    PubMed  CAS  Google Scholar 

  • Lohr M, Lensch M, André S, Kaltner H, Siebert HC, Smetana K Jr, Sinowatz F, Gabius HJ (2007) Murine homodimeric adhesion/growth-regulatory galectins-1, -2 and -7: comparative profiling of gene/promoter sequences by database mining, of expression by RT-PCR/immunohistochemistry and of contact sites for carbohydrate ligands by computational chemistry. Folia Biol (Praha) 53:109–128

    CAS  Google Scholar 

  • Matsuda-Minehata F, Inoue N, Goto Y, Manabe N (2006) The regulation of ovarian granulosa cell death by pro- and anti-apoptotic molecules. J Reprod Dev 52:695–705

    Article  PubMed  CAS  Google Scholar 

  • Moisa A, Fritz P, Eck A, Wehner HD, Mürdter T, Simon W, Gabius HJ (2007) Growth/adhesion-regulatory tissue lectin galectin-3: stromal presence but not cytoplasmic/nuclear expression in tumor cells as a negative prognostic factor in breast cancer. Anticancer Res 27:2131–2140

    PubMed  CAS  Google Scholar 

  • Nakahara S, Raz A (2007) Regulation of cancer-related gene expression by galectin-3 and the molecular mechanism of its nuclear import pathway. Cancer Metastasis Rev 26:605–610

    Article  PubMed  CAS  Google Scholar 

  • Nio J, Iwanaga T (2007) Galectins in the mouse ovary: concomitant expression of galectin-3 and progesterone degradation enzyme (20α-HSD) in the corpus luteum. J Histochem Cytochem 55:423–432

    Article  PubMed  CAS  Google Scholar 

  • Ortega N, Behonick DJ, Colnot C, Cooper DNW, Werb Z (2005) Galectin-3 is a downstream regulator of matrix metalloproteinase-9 function during endochondral bone formation. Mol Biol Cell 16:3028–3039

    Article  PubMed  CAS  Google Scholar 

  • Perez GI, Robles R, Knudson CM, Flaws JA, Korsmeyer SJ, Tilly JL (1999) Prolongation of ovarian lifespan into advanced chronological age by Bax-deficiency. Nat Genet 21:200–203

    Article  PubMed  CAS  Google Scholar 

  • Piantelli M, Iacobelli S, Almadori G, Iezzi M, Tinari N, Natoli C, Cadoni G, Lauriola L, Ranelletti FO (2002) Lack of expression of galectin-3 is associated with a poor outcome in node-negative patients with laryngeal squamous-cell carcinoma. J Clin Oncol 20:3850–3856

    Article  PubMed  CAS  Google Scholar 

  • Plzák J, Smetana K Jr, Hrdlicková E, Kodet R, Holíková Z, Liu FT, Dvořánková B, Kaltner H, Betka J, Gabius HJ (2001) Expression of galectin-3-reactive ligands in squamous cancer and normal epithelial cells as a marker of differentiation. Int J Oncol 19:59–64

    PubMed  Google Scholar 

  • Plzák J, Betka J, Smetana K Jr, Chovanec M, Kaltner H, André S, Kodet R, Gabius HJ (2004) Galectin-3—an emerging prognostic indicator in advanced head and neck carcinoma. Eur J Cancer 40:2324–2330

    Article  PubMed  Google Scholar 

  • Polyak K, Xia Y, Zweier JL, Kinzler KW, Vogelstein B (1997) A model for p53-induced apoptosis. Nature 389:300–305

    Article  PubMed  CAS  Google Scholar 

  • Ramasamy S, Duraisamy S, Barbashov S, Kawano T, Kharbanda S, Kufe D (2007) The MUC1 and galectin-3 oncoproteins function in a microRNA-dependent regulatory loop. Mol Cell 27:992–1004

    Article  PubMed  CAS  Google Scholar 

  • Rappl G, Abken H, Muche JM, Sterry W, Tilgen W, André S, Kaltner H, Ugurel S, Gabius HJ, Reinhold U (2002) CD4+CD7−leukemic T cells from patients with Sézary syndrome are protected from galectin-1-triggered T cell death. Leukemia 16:840–845

    Article  PubMed  CAS  Google Scholar 

  • Ratts VS, Flaws JA, Kolp R, Sorenson CM, Tilly JL (1995) Ablation of bcl-2 gene expression decreases the numbers of oocytes and primordial follicles established in the post-natal female mouse gonad. Endocrinology 136:3665–3668

    Article  PubMed  CAS  Google Scholar 

  • Sato Y, Suzuki T, Hidaka K, Sato H, Ito K, Ito S, Sasano H (2003) Immunolocalization of nuclear transcription factors, DAX-1 and COUP-TF II, in the normal human ovary: correlation with adrenal 4 binding protein/steroidogenic factor-1 immunolocalization during the menstrual cycle. J Clin Endocrinol Metab 88:3415–3420

    Article  PubMed  CAS  Google Scholar 

  • Saussez S, Cucu DR, Decaestecker C, Chevalier D, Kaltner H, André S, Wacreniez A, Toubeau G, Camby I, Gabius HJ, Kiss R (2006) Galectin-7 (p53-induced gene 1): a new prognostic predictor of recurrence and survival in stage IV hypopharyngeal cancer. Ann Surg Oncol 13:999–1009

    Article  PubMed  Google Scholar 

  • Sheikholeslam-Zadeh R, Decaestecker C, Delbrouck C, Danguy A, Salmon I, Zick Y, Kaltner H, Hassid S, Gabius HJ, Kiss R, Choufani G (2001) The levels of expression of galectin-3, but not of galectin-1 and galectin-8, correlate with apoptosis in human cholesteatomas. Laryngoscope 111:1042–1047

    Article  PubMed  CAS  Google Scholar 

  • Smetana K Jr, Dvořánková B, Chovanec M, Bouček J, Klíma J, Motlík J, Lensch M, Kaltner H, André S, Gabius HJ (2006) Nuclear presence of adhesion-/growth-regulatory galectins in normal/malignant cells of squamous epithelial origin. Histochem Cell Biol 125:171–182

    Article  PubMed  CAS  Google Scholar 

  • Smith ME (2001) Phagocytic properties of microglia in vitro: implications for a role in multiple sclerosis and EAE. Microsc Res Tech 54:81–94

    Article  PubMed  CAS  Google Scholar 

  • Solís D, Jiménez-Barbero J, Kaltner H, Romero A, Siebert HC, von der Lieth CW, Gabius HJ (2001) Towards defining the role of glycans as hardware in information storage and transfer: basic principles, experimental approaches and recent progress. Cells Tissues Organs 168:5–23

    Article  PubMed  Google Scholar 

  • Stierstorfer B, Kaltner H, Neumüller C, Sinowatz F, Gabius HJ (2000) Temporal and spatial regulation of expression of two galectins during kidney development of the chicken. Histochem J 32:325–336

    Article  PubMed  CAS  Google Scholar 

  • Stock M, Schäfer H, Stricker S, Gross G, Mundlos S, Otto F (2003) Expression of galectin-3 in skeletal tissues is controlled by Runx2. J Biol Chem 278:17360–17367

    Article  PubMed  CAS  Google Scholar 

  • Sturm A, Lensch M, André S, Kaltner H, Wiedenmann B, Rosewicz S, Dignass AU, Gabius HJ (2004) Human galectin-2: novel inducer of T cell apoptosis with distinct profile of caspase activation. J Immunol 173:3825–3837

    PubMed  CAS  Google Scholar 

  • Ullmann SL, Russell AJ, Mason JI, Selwood L (2003) Species differences in the ovarian distribution of 3β-hydroxysteroid dehydrogenase/Δ5 → 4 isomerase (3β-HSD) in two marsupials: the brushtail possum Trichosurus vulpecula and the grey, short-tailed opossum Monodelphis domestica. Reproduction 125:65–73

    Article  PubMed  CAS  Google Scholar 

  • Villalobo A, Nogales-González A, Gabius HJ (2006) A guide to signaling pathways connecting protein–glycan interaction with the emerging versatile effector functionality of mammalian lectins. Trends Glycosci Glycotechnol 18:1–37

    CAS  Google Scholar 

  • Walzel H, Brock J, Pöhland R, Vanselow J, Tomek W, Schneider F, Tiemann U (2004) Effects of galectin-1 on regulation of progesterone production in granulosa cells from pig ovaries in vitro. Glycobiology 14:871–881

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

The expert technical assistance of A. Helfrich, L. Mantel and C. Neumüller as well as the generous financial support of the research initiative LMUexcellent and an EC Marie Curie Research Training Network (contract 2005-019561) are greatly appreciated.

Author information

Authors and Affiliations

  1. Institute of Physiological Chemistry, Faculty of Veterinary Medicine, Ludwig Maximilians University, Munich, Germany

    Michaela Lohr, Herbert Kaltner, Martin Lensch, Sabine André & Hans-Joachim Gabius

  2. Institute of Veterinary Anatomy, Faculty of Veterinary Medicine, Ludwig Maximilians University, Munich, Germany

    Fred Sinowatz

Authors
  1. Michaela Lohr
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Herbert Kaltner
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Martin Lensch
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Sabine André
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Fred Sinowatz
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Hans-Joachim Gabius
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Herbert Kaltner.

Electronic supplementary material

Below is the link to the electronic supplementary material.

MOESM1 (DOC 116 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Lohr, M., Kaltner, H., Lensch, M. et al. Cell-type-specific expression of murine multifunctional galectin-3 and its association with follicular atresia/luteolysis in contrast to pro-apoptotic galectins-1 and -7. Histochem Cell Biol 130, 567–581 (2008). https://doi.org/10.1007/s00418-008-0465-0

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00418-008-0465-0

Keywords

Search

Navigation