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Cited by 299

The DOI matches its Crossref record; 50 of the 50 references it cites were found in a registry or an index.

Loss of pain perception in diabetes is dependent on a receptor of the immunoglobulin superfamily

Open access
Bierhaus, Angelika, Haslbeck, Karl-Matthias, Humpert, Per M., Liliensiek, Birgit, Dehmer, Thomas, Morcos, Michael, Sayed, Ahmed A.R., Andrassy, Martin, Schiekofer, Stephan, Schneider, Jochen G., Schulz, Jörg B., Heuss, Dieter, Neundörfer, Bernhard, Dierl, Stefan, Huber, Jochen, Tritschler, Hans, Schmidt, Ann-Marie, Schwaninger, Markus, Haering, Hans-Ulrich, Schleicher, Erwin, Kasper, Michael, Stern, David M., Arnold, Bernd, Nawroth, Peter P.·2004·Journal of Clinical Investigation
DOI 10.1172/jci18058
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Abstract

Molecular events that result in loss of pain perception are poorly understood in diabetic neuropathy. Our results show that the receptor for advanced glycation end products (RAGE), a receptor associated with sustained NF-kappaB activation in the diabetic microenvironment, has a central role in sensory neuronal dysfunction. In sural nerve biopsies, ligands of RAGE, the receptor itself, activated NF-kappaBp65, and IL-6 colocalized in the microvasculature of patients with diabetic neuropathy. Activation of NF-kappaB and NF-kappaB-dependent gene expression was upregulated in peripheral nerves of diabetic mice, induced by advanced glycation end products, and prevented by RAGE blockade. NF-kappaB activation was blunted in RAGE-null (RAGE(-/-)) mice compared with robust enhancement in strain-matched controls, even 6 months after diabetes induction. Loss of pain perception, indicative of long-standing diabetic neuropathy, was reversed in WT mice treated with soluble RAGE. Most importantly, loss of pain perception was largely prevented in RAGE(-/-) mice, although they were not protected from diabetes-induced loss of PGP9.5-positive plantar nerve fibers. These data demonstrate, for the first time to our knowledge, that the RAGE-NF-kappaB axis operates in diabetic neuropathy, by mediating functional sensory deficits, and that its inhibition may provide new therapeutic approaches.

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Research works printed but not linked: 7

  1. 10.1002/(SICI)1096-9136(1998120)15:4+<s57::aid-dia741>3.3.CO;2-4</s57::aid-dia741> · doi:10.1002/(sici)1096-9136(1998120)15:4+<s57::aid-dia741>3.3.co;2-4</s57::aid-dia741>
  2. Carrington, 1999, Diabetes Reviews., 7, 275
  3. 10.1016/S0006-8993(99)01670-4 · doi:10.1016/s0006-8993(99)01670-4
  4. 10.1007/s00401-002-0518-8 · doi:10.1007/s00401-002-0518-8
  5. Schmidt, 2001, J. Clin. Invest., 108, 949, 10.1172/JCI200114002 · DOI
  6. Liliensiek, 2004, J. Clin. Invest., 113, 1641, 10.1172/JCI200418704 · DOI
  7. Neundörfer, 1998, Dtsch. Med. Wochenschr., 23, 1519, 10.1055/s-2007-1023888 · doi:10.1055/s-2007-1023888

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Metadata

Authors
Bierhaus, A., Haslbeck, K.-M., Humpert, P. M., Liliensiek, B., Dehmer, T., Morcos, M., Sayed, A. A. R., Andrassy, M., Schiekofer, S., Schneider, J. G., Schulz, J. B., Heuss, D., Neundörfer, B., Dierl, S., Huber, J., Tritschler, H., Schmidt, A.-M., Schwaninger, M., Haering, H.-U., Schleicher, E., Kasper, M., Stern, D. M., Arnold, B., & Nawroth, P. P.
Venue
Journal of Clinical Investigation
Publisher
American Society for Clinical Investigation
Published
2004-12-15
Volume
114
Issue
12
Pages
1741-1751
ISSN
0021-9738 (ISSN-L)
DOI
10.1172/jci18058
OpenAlex
W2162666481
Cited by
299
References
50
FWCI
10.26
Type
journal article
Language
en
Open access
bronze

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CoChat. (2026). Citation check: Loss of pain perception in diabetes is dependent on a receptor of the immunoglobulin superfamily. https://app.cochat.ai/papers/10.1172/jci18058
The paper
Bierhaus, A., Haslbeck, K.-M., Humpert, P. M., Liliensiek, B., Dehmer, T., Morcos, M., Sayed, A. A. R., Andrassy, M., Schiekofer, S., Schneider, J. G., Schulz, J. B., Heuss, D., Neundörfer, B., Dierl, S., Huber, J., Tritschler, H., Schmidt, A.-M., Schwaninger, M., Haering, H.-U., . . . Nawroth, P. P. (2004). Loss of pain perception in diabetes is dependent on a receptor of the immunoglobulin superfamily. Journal of Clinical Investigation. https://doi.org/10.1172/jci18058

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Bibliographic data: Semantic Scholar, OpenAlex, Crossref.

Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.