Accelerated diabetic glomerulopathy in galectin-3/AGE receptor 3 knockout mice

Giuseppe Pugliese, Flavia Pricci, Carla Iacobini, Gaetano Leto, Lorena Amadio, Paola Barsotti, Luciano Frigeri, Dan K. Hsu, Helen Vlassara, Fu-Tong Liu, Umberto Di Mario

Research output: Contribution to journalArticle

148 Citations (Scopus)

Abstract

Several molecules were shown to bind advanced glycation end products (AGEs) in vitro, but it is not known whether they all serve as AGE receptors and which functional role they play in vivo. We investigated the role of galectin-3, a multifunctional lectin with (anti)adhesive and growth-regulating properties, as an AGE receptor and its contribution to the development of diabetic glomerular disease, using a knockout mouse model. Galectin-3 knockout mice obtained by gene ablation and the corresponding wild-type mice were rendered diabetic with streptozotocin and killed 4 months later, together with age-matched nondiabetic controls. Despite a comparable degree of metabolic derangement, galectin-3-deficient mice developed accelerated glomerulopathy vs. the wild-type animals, as evidenced by the more pronounced increase in proteinuria, extracellular matrix gene expression, and mesangial expansion. This was associated with a more marked renal/glomerular AGE accumulation, indicating it was attributable to the lack of galectin-3 AGE receptor function. The galectin-3-deficient genotype was associated with reduced expression of receptors implicated in AGE removal (macrophage scavenger receptor A and AGE-R1) and increased expression of those mediating cell activation (RAGE and AGE-R2). These results show that the galectin-3-regulated AGE receptor pathway is operating in vivo and protects toward AGE-induced tissue injury in contrast to that through RAGE.

Original languageEnglish (US)
Pages (from-to)2471-2479
Number of pages9
JournalFASEB Journal
Volume15
Issue number13
DOIs
StatePublished - 2001

Fingerprint

glomerulopathy
Galectin 3
Knockout Mice
receptors
mice
Scavenger Receptors
Advanced Glycosylation End Products
Wild Animals
streptozotocin
Streptozocin
Ablation
Proteinuria
extracellular matrix
Lectins
Gene expression
lectins
adhesives
Adhesives
Extracellular Matrix
Advanced Glycosylation End Product-Specific Receptor

Keywords

  • Advanced glycation end product receptors
  • Advanced glycation end products
  • Diabetic nephropathy
  • Extracellular matrix

ASJC Scopus subject areas

  • Agricultural and Biological Sciences (miscellaneous)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry
  • Cell Biology

Cite this

Pugliese, G., Pricci, F., Iacobini, C., Leto, G., Amadio, L., Barsotti, P., ... Di Mario, U. (2001). Accelerated diabetic glomerulopathy in galectin-3/AGE receptor 3 knockout mice. FASEB Journal, 15(13), 2471-2479. https://doi.org/10.1096/fj.01-0006com

Accelerated diabetic glomerulopathy in galectin-3/AGE receptor 3 knockout mice. / Pugliese, Giuseppe; Pricci, Flavia; Iacobini, Carla; Leto, Gaetano; Amadio, Lorena; Barsotti, Paola; Frigeri, Luciano; Hsu, Dan K.; Vlassara, Helen; Liu, Fu-Tong; Di Mario, Umberto.

In: FASEB Journal, Vol. 15, No. 13, 2001, p. 2471-2479.

Research output: Contribution to journalArticle

Pugliese, G, Pricci, F, Iacobini, C, Leto, G, Amadio, L, Barsotti, P, Frigeri, L, Hsu, DK, Vlassara, H, Liu, F-T & Di Mario, U 2001, 'Accelerated diabetic glomerulopathy in galectin-3/AGE receptor 3 knockout mice', FASEB Journal, vol. 15, no. 13, pp. 2471-2479. https://doi.org/10.1096/fj.01-0006com
Pugliese G, Pricci F, Iacobini C, Leto G, Amadio L, Barsotti P et al. Accelerated diabetic glomerulopathy in galectin-3/AGE receptor 3 knockout mice. FASEB Journal. 2001;15(13):2471-2479. https://doi.org/10.1096/fj.01-0006com
Pugliese, Giuseppe ; Pricci, Flavia ; Iacobini, Carla ; Leto, Gaetano ; Amadio, Lorena ; Barsotti, Paola ; Frigeri, Luciano ; Hsu, Dan K. ; Vlassara, Helen ; Liu, Fu-Tong ; Di Mario, Umberto. / Accelerated diabetic glomerulopathy in galectin-3/AGE receptor 3 knockout mice. In: FASEB Journal. 2001 ; Vol. 15, No. 13. pp. 2471-2479.
@article{1c7d1d5a688e4dbf9d46087636f862fe,
title = "Accelerated diabetic glomerulopathy in galectin-3/AGE receptor 3 knockout mice",
abstract = "Several molecules were shown to bind advanced glycation end products (AGEs) in vitro, but it is not known whether they all serve as AGE receptors and which functional role they play in vivo. We investigated the role of galectin-3, a multifunctional lectin with (anti)adhesive and growth-regulating properties, as an AGE receptor and its contribution to the development of diabetic glomerular disease, using a knockout mouse model. Galectin-3 knockout mice obtained by gene ablation and the corresponding wild-type mice were rendered diabetic with streptozotocin and killed 4 months later, together with age-matched nondiabetic controls. Despite a comparable degree of metabolic derangement, galectin-3-deficient mice developed accelerated glomerulopathy vs. the wild-type animals, as evidenced by the more pronounced increase in proteinuria, extracellular matrix gene expression, and mesangial expansion. This was associated with a more marked renal/glomerular AGE accumulation, indicating it was attributable to the lack of galectin-3 AGE receptor function. The galectin-3-deficient genotype was associated with reduced expression of receptors implicated in AGE removal (macrophage scavenger receptor A and AGE-R1) and increased expression of those mediating cell activation (RAGE and AGE-R2). These results show that the galectin-3-regulated AGE receptor pathway is operating in vivo and protects toward AGE-induced tissue injury in contrast to that through RAGE.",
keywords = "Advanced glycation end product receptors, Advanced glycation end products, Diabetic nephropathy, Extracellular matrix",
author = "Giuseppe Pugliese and Flavia Pricci and Carla Iacobini and Gaetano Leto and Lorena Amadio and Paola Barsotti and Luciano Frigeri and Hsu, {Dan K.} and Helen Vlassara and Fu-Tong Liu and {Di Mario}, Umberto",
year = "2001",
doi = "10.1096/fj.01-0006com",
language = "English (US)",
volume = "15",
pages = "2471--2479",
journal = "FASEB Journal",
issn = "0892-6638",
publisher = "FASEB",
number = "13",

}

TY - JOUR

T1 - Accelerated diabetic glomerulopathy in galectin-3/AGE receptor 3 knockout mice

AU - Pugliese, Giuseppe

AU - Pricci, Flavia

AU - Iacobini, Carla

AU - Leto, Gaetano

AU - Amadio, Lorena

AU - Barsotti, Paola

AU - Frigeri, Luciano

AU - Hsu, Dan K.

AU - Vlassara, Helen

AU - Liu, Fu-Tong

AU - Di Mario, Umberto

PY - 2001

Y1 - 2001

N2 - Several molecules were shown to bind advanced glycation end products (AGEs) in vitro, but it is not known whether they all serve as AGE receptors and which functional role they play in vivo. We investigated the role of galectin-3, a multifunctional lectin with (anti)adhesive and growth-regulating properties, as an AGE receptor and its contribution to the development of diabetic glomerular disease, using a knockout mouse model. Galectin-3 knockout mice obtained by gene ablation and the corresponding wild-type mice were rendered diabetic with streptozotocin and killed 4 months later, together with age-matched nondiabetic controls. Despite a comparable degree of metabolic derangement, galectin-3-deficient mice developed accelerated glomerulopathy vs. the wild-type animals, as evidenced by the more pronounced increase in proteinuria, extracellular matrix gene expression, and mesangial expansion. This was associated with a more marked renal/glomerular AGE accumulation, indicating it was attributable to the lack of galectin-3 AGE receptor function. The galectin-3-deficient genotype was associated with reduced expression of receptors implicated in AGE removal (macrophage scavenger receptor A and AGE-R1) and increased expression of those mediating cell activation (RAGE and AGE-R2). These results show that the galectin-3-regulated AGE receptor pathway is operating in vivo and protects toward AGE-induced tissue injury in contrast to that through RAGE.

AB - Several molecules were shown to bind advanced glycation end products (AGEs) in vitro, but it is not known whether they all serve as AGE receptors and which functional role they play in vivo. We investigated the role of galectin-3, a multifunctional lectin with (anti)adhesive and growth-regulating properties, as an AGE receptor and its contribution to the development of diabetic glomerular disease, using a knockout mouse model. Galectin-3 knockout mice obtained by gene ablation and the corresponding wild-type mice were rendered diabetic with streptozotocin and killed 4 months later, together with age-matched nondiabetic controls. Despite a comparable degree of metabolic derangement, galectin-3-deficient mice developed accelerated glomerulopathy vs. the wild-type animals, as evidenced by the more pronounced increase in proteinuria, extracellular matrix gene expression, and mesangial expansion. This was associated with a more marked renal/glomerular AGE accumulation, indicating it was attributable to the lack of galectin-3 AGE receptor function. The galectin-3-deficient genotype was associated with reduced expression of receptors implicated in AGE removal (macrophage scavenger receptor A and AGE-R1) and increased expression of those mediating cell activation (RAGE and AGE-R2). These results show that the galectin-3-regulated AGE receptor pathway is operating in vivo and protects toward AGE-induced tissue injury in contrast to that through RAGE.

KW - Advanced glycation end product receptors

KW - Advanced glycation end products

KW - Diabetic nephropathy

KW - Extracellular matrix

UR - http://www.scopus.com/inward/record.url?scp=17944369113&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=17944369113&partnerID=8YFLogxK

U2 - 10.1096/fj.01-0006com

DO - 10.1096/fj.01-0006com

M3 - Article

C2 - 11689472

AN - SCOPUS:17944369113

VL - 15

SP - 2471

EP - 2479

JO - FASEB Journal

JF - FASEB Journal

SN - 0892-6638

IS - 13

ER -