CoChat
Sign Up
Cited by 229Advanced Glycation End Products researchChronic Kidney Disease and DiabetesDialysis and Renal Disease Management

Advanced glycation endproduct (AGE) receptor 1 is a negative regulator of the inflammatory response to AGE in mesangial cells

Open access
Lu, Changyong, He, John Cijiang, Cai, Weijing, Liu, Huixian, Zhu, Li, Vlassara, Helen·2004·Proceedings of the National Academy of Sciences
DOI 10.1073/pnas.0401588101PMC PMC511050
Open this paper in CoChat — free account

Abstract

Advanced glycation endproducts (AGE) contribute to kidney disease due to diabetes or aging by means of mesangial cell (MC) receptors, such as the receptor for AGE (RAGE), which promote oxidant-stress-dependent NF-kappaB activation and inflammatory gene expression. MC also express scavenger receptors SR-I and SR-II and AGE receptors 1, 2, and 3 (AGE-R1, -R2, and -R3), some of which are linked to AGE turnover. Because AGE-R1 expression is found suppressed in severe diabetic kidney disease, as other receptors increase, we investigated whether his molecule has a protective role against AGE-induced MC injury. A stable murine MC line overexpressing AGE-R1 (R1-MC) was generated, exhibiting a 1.8- to 2.7-fold increase in (125)I-AGE-specific binding, uptake, and degradation, compared with mock-MC. However, AGE-stimulated NF-kappaB activity and mitogen-activated protein kinase (MAPK) (p44/42) phosphorylation were found markedly suppressed in R1-MC. Additionally, AGE-stimulated macrophage chemotaxis protein 1 and RAGE overexpression were abolished in R1-MC. The effect of R1 on RAGE signaling was investigated after overexpressing RAGE in Chinese hamster ovary cells, which lack RAGE. AGE stimulation elicited NF-kappaB and MAPK activities in RAGE-Chinese hamster ovary cells; however, after cotransfection with R1, these responses were suppressed. Also, after silencing endogenous R1 in wild-type MC by R1 small interfering RNA, AGE-mediated MAPK/p44/42 activation exceeded by >2-fold that of mock-MC, consistent with loss of the activation-inhibitory properties of native AGE-R1. AGE-R1, although enhancing AGE removal, is also a distinct receptor in that it suppresses AGE-mediated MC inflammatory injury through negative regulation of RAGE, a previously uncharacterized pathway that may protect renal and other tissue injury due to diabetes and aging.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1073/pnas.0401588101

Cites

48 of 48 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Linoleic acid concentration in blood lipids or granulocytes is not associated with CRP or IL-6 concentration.

    “The concentration of linoleic acid in blood lipids (578,579) or granulocytes (374) was not associated with CRP or IL-6 concentration”

    From Dietary factors and low-grade inflammation in relation to overweight and obesity (2011) · cites this paper as [578]

  • In an Italian study, alpha-linolenic acid in plasma fatty acids is inversely associated with CRP.

    “Data from an Italian study showed no association between a-linolenic acid in plasma fatty acids and several cytokines including IL-6 and TNF-a, but there was an inverse association with CRP (578)”

    From Dietary factors and low-grade inflammation in relation to overweight and obesity (2011) · cites this paper as [578]

  • In an Italian study, alpha-linolenic acid in plasma fatty acids is not associated with several cytokines including IL-6 and TNF-a.

    “Data from an Italian study showed no association between a-linolenic acid in plasma fatty acids and several cytokines including IL-6 and TNF-a, but there was an inverse association with CRP (578)”

    From Dietary factors and low-grade inflammation in relation to overweight and obesity (2011) · cites this paper as [578]

  • In Ferrucci et al., plasma arachidonic acid is not associated with CRP, TNF-a, IL-1b, IL-10 or sIL-6R concentrations.

    “Ferrucci et al. (578) reported no association between arachidonic acid in plasma and CRP, TNF-a, IL-1b, IL-10 and sIL-6R concentrations, while there was an inverse association with IL-6 and IL-1ra concentrations and a positive association with TGF-b”

    From Dietary factors and low-grade inflammation in relation to overweight and obesity (2011) · cites this paper as [578]

  • In an elderly Italian population, plasma EPA is inversely associated with IL-6 concentration and positively associated with IL-10 and TGFb concentrations.

    “In an elderly Italian population, plasma EPA was inversely associated with IL-6 concentration and positively associated with the concentrations of the anti-inflammatory cytokines IL-10 and TGFb (578) .”

    From Dietary factors and low-grade inflammation in relation to overweight and obesity (2011) · cites this paper as [578]

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Research works printed but not linked: 48

  1. [1]Vlassara, H. (2001) Diabetes Metab. Res. Rev. 17, 436–443. [DOI] [PubMed] [Google Scholar]
  2. [2]Schmidt, A. M., Yan, S. D., Yan, S. F. & Stern, D. M. (2001) J. Clin. Invest. 108, 949–955. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. [3]Finkel, T. & Holbrook, N. J. (2000) Nature 408, 239–247. [DOI] [PubMed] [Google Scholar]
  4. [4]Kislinger, T., Tanji, N., Wendt, T., Qu, W., Lu, Y., Ferran, L. J., Jr., Taguchi, A., Olson, K., Bucciarelli, L., Goova, M., et al. (2001) Arterioscler. Thromb. Vasc. Biol. 21, 905–910. [DOI] [PubMed] [Google Scholar]
  5. [5]Koschinsky, T., He, C. J., Mitsuhashi, T., Bucala, R., Liu, C., Buenting, C., Heitmann, K. & Vlassara, H. (1997) Proc. Natl. Acad. Sci. USA 94, 6474–6479. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. [6]He, C., Sabol, J., Mitsuhashi, T. & Vlassara, H. (1999) Diabetes 48, 1308–1315. [DOI] [PubMed] [Google Scholar]
  7. [7]Hofmann, M. A., Drury, S., Fu, C., Qu, W., Taguchi, A., Lu, Y., Avila, C., Kambham, N., Bierhaus, A., Nawroth, P., et al. (1999) Cell 97, 889–901. [DOI] [PubMed] [Google Scholar]
  8. [8]Wautier, M. P., Chappey, O., Corda, S., Stern, D. M., Schmidt, A. M. & Wautier, J. L. (2001) Am. J. Physiol. 280, E685–E694. [DOI] [PubMed] [Google Scholar]
  9. [9]Basta, G., Lazzerini, G., Massaro, M., Simoncini, T., Tanganelli, P., Fu, C., Kislinger, T., Stern, D. M., Schmidt, A. M. & De Caterina, R. (2002) Circulation 105, 816–822. [DOI] [PubMed] [Google Scholar]
  10. [10]Suzuki, H., Kurihara, Y., Takeya, M., Kamada, N., Kataoka, M., Jishage, K., Ueda, O., Sakaguchi, H., Higashi, T., Suzuki, T., et al. (1997) Nature 386, 292–296. [DOI] [PubMed] [Google Scholar]
  11. [11]Miyazaki, A., Nakayama, H. & Horiuchi, S. (2002) Trends Cardiovasc. Med. 12, 258–262. [DOI] [PubMed] [Google Scholar]
  12. [12]Vlassara, H., Li, Y. M., Imani, F., Wojciechowicz, D., Yang, Z., Liu, F. T. & Cerami, A. (1995) Mol. Med. 1, 634–646. [PMC free article] [PubMed] [Google Scholar]
  13. [13]Li, Y. M., Mitsuhashi, T., Wojciechowicz, D., Shimizu, N., Li, J., Stitt, A., He, C., Banerjee, D. & Vlassara, H. (1996) Proc. Natl. Acad. Sci. USA 93, 11047–11052. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. [14]Pugliese, G., Pricci, F., Iacobini, C., Leto, G., Amadio, L., Barsotti, P., Frigeri, L., Hsu, D. K., Vlassara, H., Liu, F. T. & Di Mario, U. (2001) FASEB J. 15, 2471–2479. [DOI] [PubMed] [Google Scholar]
  15. [15]He, C. J., Koschinsky, T., Buenting, C. & Vlassara, H. (2001) Mol. Med. 7, 159–168. [PMC free article] [PubMed] [Google Scholar]
  16. [16]Vlassara, H., Striker, L. J., Teichberg, S., Fuh, H., Li, Y. M. & Steffes, M. (1994) Proc. Natl. Acad. Sci. USA 91, 11704–11708. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. [17]Li, Y. M., Steffes, M., Donnelly, T., Liu, C., Fuh, H., Basgen, J., Bucala, R. & Vlassara, H. (1996) Proc. Natl. Acad. Sci. USA 93, 3902–3907. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. [18]Fioretto, P., Steffes, M. W., Sutherland, D. E. & Mauer, M. (1995) Kidney Int. 48, 1929–1935. [DOI] [PubMed] [Google Scholar]
  19. [19]Skolnik, E. Y., Yang, Z., Makita, Z., Radoff, S., Kirstein, M. & Vlassara, H. (1991) J. Exp. Med. 174, 931–939. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. [20]Doi, T., Vlassara, H., Kirstein, M., Yamada, Y., Striker, G. E. & Striker, L. J. (1992) Proc. Natl. Acad. Sci. USA 89, 2873–2877. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. [21]Yang, C. W., Vlassara, H., Peten, E. P., He, C. J., Striker, G. E. & Striker, L. J. (1994) Proc. Natl. Acad. Sci. USA 91, 9436–9440. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. [22]Yang, C. W., Vlassara, H., Striker, G. E. & Striker, L. J. (1995) Kidney Int. Suppl. 49, S55–S58. [PubMed] [Google Scholar]
  23. [23]Brett, J., Schmidt, A. M., Yan, S. D., Zou, Y. S., Weidman, E., Pinsky, D., Nowygrod, R., Neeper, M., Przysiecki, C., Shaw, A., et al. (1993) Am. J. Pathol. 143, 1699–1712. [PMC free article] [PubMed] [Google Scholar]
  24. [24]Tanji, N., Markowitz, G. S., Fu, C., Kislinger, T., Taguchi, A., Pischetsrieder, M., Stern, D., Schmidt, A. M. & D'Agati, V. D. (2000) J. Am. Soc. Nephrol. 11, 1656–1666. [DOI] [PubMed] [Google Scholar]
  25. [25]He, C. J., Zheng, F., Stitt, A., Striker, L., Hattori, M. & Vlassara, H. (2000) Kidney Int. 58, 1931–1940. [DOI] [PubMed] [Google Scholar]
  26. [26]Vlassara, H., Brownlee, M. & Cerami, A. (1985) Proc. Natl. Acad. Sci. USA 82, 5588–5592. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. [27]Sioud, M. (2004) Trends Pharmacol. Sci. 25, 22–28. [DOI] [PubMed] [Google Scholar]
  28. [28]Banba, N., Nakamura, T., Matsumura, M., Kuroda, H., Hattori, Y. & Kasai, K. (2000) Kidney Int. 58, 684–690. [DOI] [PubMed] [Google Scholar]
  29. [29]Cerami, C., Founds, H., Nicholl, I., Mitsuhashi, T., Giordano, D., Vanpatten, S., Lee, A., Al-Abed, Y., Vlassara, H., Bucala, R. & Cerami, A. (1997) Proc. Natl. Acad. Sci. USA 94, 13915–13920. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. [30]Kislinger, T., Fu, C., Huber, B., Qu, W., Taguchi, A., Du Yan, S., Hofmann, M., Yan, S. F., Pischetsrieder, M., Stern, D. & Schmidt, A. M. (1999) J. Biol. Chem. 274, 31740–31749. [DOI] [PubMed] [Google Scholar]
  31. [31]Yamagishi, S., Inagaki, Y., Okamoto, T., Amano, S., Koga, K., Takeuchi, M. & Makita, Z. (2002) J. Biol. Chem. 277, 20309–20315. [DOI] [PubMed] [Google Scholar]
  32. [32]Lal, M. A., Brismar, H., Eklof, A. C. & Aperia, A. (2002) Kidney Int. 61, 2006–2014. [DOI] [PubMed] [Google Scholar]
  33. [33]Tsuji, H., Iehara, N., Masegi, T., Imura, M., Ohkawa, J., Arai, H., Ishii, K., Kita, T. & Doi, T. (1998) Biochem. Biophys. Res. Commun. 245, 583–588. [DOI] [PubMed] [Google Scholar]
  34. [34]Iwashima, Y., Eto, M., Horiuchi, S. & Sano, H. (1999) Biochem. Biophys. Res. Commun. 264, 441–448. [DOI] [PubMed] [Google Scholar]
  35. [35]Scivittaro, V., Ganz, M. B. & Weiss, M. F. (2000) Am. J. Physiol. 278, F676–F683. [DOI] [PubMed] [Google Scholar]
  36. [36]Lander, H. M., Tauras, J. M., Ogiste, J. S., Hori, O., Moss, R. A. & Schmidt, A. M. (1997) J. Biol. Chem. 272, 17810–17814. [DOI] [PubMed] [Google Scholar]
  37. [37]Yeh, C. H., Sturgis, L., Haidacher, J., Zhang, X. N., Sherwood, S. J., Bjercke, R. J., Juhasz, O., Crow, M. T., Tilton, R. G. & Denner, L. (2001) Diabetes 50, 1495–1504. [DOI] [PubMed] [Google Scholar]
  38. [38]Huang, J. S., Guh, J. Y., Chen, H. C., Hung, W. C., Lai, Y. H. & Chuang, L. Y. (2001) J. Cell Biochem. 81, 102–113. [DOI] [PubMed] [Google Scholar]
  39. [39]Satoh, H., Togo, M., Hara, M., Miyata, T., Han, K., Maekawa, H., Ohno, M., Hashimoto, Y., Kurokawa, K. & Watanabe, T. (1997) Biochem. Biophys. Res. Commun. 239, 111–115. [DOI] [PubMed] [Google Scholar]
  40. [40]Rovin, B. H., Dickerson, J. A., Tan, L. C. & Hebert, C. A. (1995) Kidney Int. 48, 1263–1271. [DOI] [PubMed] [Google Scholar]
  41. [41]Hisada, Y., Sakurai, H. & Sugaya, T. (2000) Biochem. Biophys. Res. Commun. 269, 309–316. [DOI] [PubMed] [Google Scholar]
  42. [42]Lynn, E. G., Siow, Y. L., Frohlich, J., Cheung, G. T. & O, K. (2001) Kidney Int. 60, 520–532. [DOI] [PubMed] [Google Scholar]
  43. [43]Ha, H., Yu, M. R., Choi, Y. J., Kitamura, M. & Lee, H. B. (2002) J. Am. Soc. Nephrol. 13, 894–902. [DOI] [PubMed] [Google Scholar]
  44. [44]Tanaka, N., Yonekura, H., Yamagishi, S., Fujimori, H., Yamamoto, Y. & Yamamoto, H. (2000) J. Biol. Chem. 275, 25781–25790. [DOI] [PubMed] [Google Scholar]
  45. [45]Soulis, T., Thallas, V., Youssef, S., Gilbert, R. E., McWilliam, B. G., Murray-McIntosh, R. P. & Cooper, M. E. (1997) Diabetologia 40, 619–628. [DOI] [PubMed] [Google Scholar]
  46. [46]Arnalich, F., Hernanz, A., Lopez-Maderuelo, D., De la Fuente, M., Arnalich, F. M., Andres-Mateos, E., Fernandez-Capitan, C. & Montiel, C. (2001) Free Radical Res. 35, 873–884. [DOI] [PubMed] [Google Scholar]
  47. [47]Cai, W., Gao, Q. D., Zhu, L., Peppa, M., He, C. & Vlassara, H. (2002) Mol. Med. 8, 337–346. [PMC free article] [PubMed] [Google Scholar]
  48. [48]Furuta, T., Saito, T., Ootaka, T., Soma, J., Obara, K., Abe, K. & Yoshinaga, K. (1993) Am. J. Kidney Dis. 21, 480–485. [DOI] [PubMed] [Google Scholar]

Cited by

Sorted by citations

Related

Authors
Lu, C., He, J. C., Cai, W., Liu, H., Zhu, L., & Vlassara, H.
Affiliations
  • Mount Sinai Health System (US)
  • Department of Geriatrics and Adult Development, Division of Experimental Diabetes and Aging, and Department of Medicine, Division of Nephrology, Mount Sinai School of Medicine, New York, NY 10029
Corresponding author
Vlassara, Helen
ORCID
Liu, Huixian
Venue
Proceedings of the National Academy of Sciences
Publisher
National Academy of Sciences
Published
2004-08-02
Volume
101
Issue
32
Pages
11767-11772
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
DOI
10.1073/pnas.0401588101
PMC
PMC511050
OpenAlex
W2030022427
Cited by
228
References
48
Citations by year
2026: 3 · 2025: 5 · 2024: 8 · 2023: 6 · 2022: 7 · 2021: 13 · 2020: 11 · 2019: 8 · 2018: 9 · 2017: 15 · 2016: 13 · 2015: 15 · 2014: 8 · 2013: 13 · 2012: 16
FWCI
7.46
Type
journal article
Language
en
Open access
Locations
  • Proceedings of the National Academy of Sciences (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health
  • National Institute of Diabetes and Digestive and Kidney Diseases (R01DK054788, DK54788)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Advanced Glycation End Products research
  • Health Sciences › Medicine › Nephrology › Chronic Kidney Disease and Diabetes
  • Health Sciences › Medicine › Nephrology › Dialysis and Renal Disease Management
Keywords
advanced glycation end products, receptor for advanced glycation end products, mesangial cells, diabetic nephropathy, inflammation, NF-κB signaling, kidney injury
MeSH terms
Receptor for Advanced Glycation End Products, Animals, Cell Line, Gene Expression Regulation, Glomerular Mesangium, Humans, Inflammation, Phosphorylation, Receptors, Immunologic, Transfection, Signal Transduction, NF-kappa B, Glycation End Products, Advanced, Chemokine CCL2, COS Cells, Mitogen-Activated Protein Kinase 1, Mitogen-Activated Protein Kinases, Mitogen-Activated Protein Kinase 3, Mice

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review