Identification of Galectin-3 As a High-Affinity Binding Protein for Advanced Glycation End Products (AGE): A New Member of the AGE-Receptor Complex

Vlassara, Helen; Li, Yong Ming; Imani, Farhad; Wojciechowicz, Donald; Yang, Zhi; Liu, Fu‐Tong; Cerami, Anthony

doi:10.1007/bf03401604

Cited by 378 publications

(253 citation statements)

References 42 publications

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“…Because the interaction between AGEs and Gal-3 also involves the CRD, Gal-3 multimerization in response to HG or AGEs could be a consequence of the increased Gal-3 expression and binding induced by AGEs. Moreover, it is compatible with the reported Gal-3 AGE-receptor function, as shown in monocytes-macrophages (6).…”

Section: Discussionsupporting

confidence: 90%

The diabetic milieu modulates the advanced glycation end product-receptor complex in the mesangium by inducing or upregulating galectin-3 expression.

et al. 2000

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Nonenzymatic glycation has been implicated in the pathogenesis of the dysregulated tissue remodeling that characterizes diabetic glomerulopathy, via the formation of advanced glycation end products (AGEs) and their binding to cell surface receptors. Several AGEbinding proteins have been identified so far, including p60, p90, and the adhesive and growth-regulating lectin galectin-3 (Gal-3), the components of the so-called AGEreceptor complex. This study aimed to evaluate the mesangial expression of the AGE-receptor complex and its modulation by the diabetic milieu, both in vivo, in nondiabetic versus streptozotocin-induced diabetic rats, and in vitro, in mesangial cells exposed to either normal glucose (NG) levels (5.5 mmol/l), as compared with high glucose (HG) levels (30 mmol/l) and iso-osmolar mannitol (M), or to native bovine serum albumin (BSA), as compared with glycated BSA with AGE formation (BSA-AGE) and glycated BSA in which AGE formation was prevented by aminoguanidine (BSA-AM). In vivo, Gal-3 protein and mRNA were not detectable in glomeruli from nondiabetic rats until 12 months after initiating the study. On the contrary, in diabetic rats, Gal-3 expression was observed at 2 months of disease duration, and it increased thereafter. Both p60 and p90 immunoreactivities were observed at the glomerular level with slightly increased expression of p90, but not p60, in diabetic versus nondiabetic animals. In vitro, Gal-3 was not detectable in mesangial cells cultured in NG (although it became evident after a certain number of passages in culture), whereas Gal-3 was detectable in cells grown on BSA. Prolonged exposure (2-4 weeks) of mesangial cells to HG but not to M, as well as growing cells on BSA-AGE and, to a lesser extent, BSA-AM, induced or significantly increased the expression of Gal-3, both protein (up to 2.65-fold) and mRNA (up to 3.10-fold) and its secretion in the medium (by ~50%). Both p60 and p90 were demonstrated in mesangial cells under NG conditions, and the expression of p90, but not p60, was upregulated by ~20% by HG or BSA-AGE. These results indicate that 1) under basal conditions, Gal-3, unlike p90 and p60, is not detectable in the mesangium but becomes expressed with aging and 2) the diabetic milieu induces or upregulates Gal-3 production, whereas it increases only slightly the expression of p90, but not p60. Gal-3 expression or overexpression may modulate the AGE-receptor-mediated events by modifying the function of the AGE-receptor complex. Additionally, it may exert direct effects on tissue remodeling by virtue of its adhesive and growthregulating properties.

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Section: Discussionsupporting

confidence: 90%

The diabetic milieu modulates the advanced glycation end product-receptor complex in the mesangium by inducing or upregulating galectin-3 expression.

et al. 2000

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“…Importantly, the binding affinity of AGE-BSA to FEEL-1 and FEEL-2 cells appeared to exceed that to other receptors for AGEs. Calculated K d was 25 nM for FFEL-2; 39 nM for FEEL-1; 85 nM for CD36 (14); 100 nM for RAGE (9); 126 nM for SR-BI (13); 148 nM for lectin-like oxidized low density lipoprotein receptor-1 (15); and 350 nM for galectin3 (11), assuming that molecular mass of AGE-BSA is 66 kDa. The binding activity of CHO-FEEL-1 cells was ϳ20-fold lower than that of CHO-FEEL-2 cells.…”

Section: Discussionmentioning

confidence: 99%

“…The AGE-elicited proinflammatory reactions are mediated by its receptors or binding proteins, which include the receptor for advanced glycation end product (RAGE) (9,10), OST-48 (ARE-R1)/80K-H (AGE-R2)/galectin-3 (AGE-R3) (11), scavenger receptor class AI/AII (SR-A) (12), scavenger receptor class B type I (SR-BI) (13), cell surface glycoprotein CD36 (14), lectin-like oxidized low density lipoprotein receptor-1 (15), lactoferin (16), and lysozyme (16).…”

mentioning

confidence: 99%

FEEL-1 and FEEL-2 Are Endocytic Receptors for Advanced Glycation End Products

Tamura

Adachi

Osuga

et al. 2003

Journal of Biological Chemistry

185

136

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“…More recently one of these receptors has been shown to have homology with the protein, galectin-3 [52]. The role of these AGE binding proteins has not been fully delineated.…”

Section: Discussionmentioning

confidence: 99%

Advanced glycation end products and their receptors co-localise in rat organs susceptible to diabetic microvascular injury

et al. 1997

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Identification of Galectin-3 As a High-Affinity Binding Protein for Advanced Glycation End Products (AGE): A New Member of the AGE-Receptor Complex

Cited by 378 publications

References 42 publications

The diabetic milieu modulates the advanced glycation end product-receptor complex in the mesangium by inducing or upregulating galectin-3 expression.

The diabetic milieu modulates the advanced glycation end product-receptor complex in the mesangium by inducing or upregulating galectin-3 expression.

FEEL-1 and FEEL-2 Are Endocytic Receptors for Advanced Glycation End Products

Advanced glycation end products and their receptors co-localise in rat organs susceptible to diabetic microvascular injury

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