Receptor-dependent cell stress and amyloid accumulation in systemic amyloidosis.
Accumulation of fibrils composed of amyloid A in tissues resulting in displacement of normal structures and cellular dysfunction is the characteristic feature of systemic amyloidoses. Here we show that RAGE, a multiligand immunoglobulin superfamily cell surface molecule, is a receptor for the amyloidogenic form of serum amyloid A. Interactions between RAGE and amyloid A induced cellular perturbation. In a mouse model, amyloid A accumulation, evidence of cell stress and expression of RAGE were closely linked. Antagonizing RAGE suppressed cell stress and amyloid deposition in mouse spleens. These data indicate that RAGE is a potential target for inhibiting accumulation of amyloid A and for limiting cellular dysfunction induced by amyloid A.
Yan
S D
SD
Departments of Pathology, Physiology, and Surgery, College of Physicians and Surgeons of Columbia University, New York, New York 10032, USA. sdy1@columbia.edu
Zhu
H
H
Zhu
A
A
Golabek
A
A
Du
H
H
Roher
A
A
Yu
J
J
Soto
C
C
Schmidt
A M
AM
Stern
D
D
Kindy
M
M
D000682:Amyloid / Q000378:metabolism; D000686:Amyloidosis / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D002460:Cell Line; D006023:Glycoproteins / Q000378:metabolism / Q000494:pharmacology; D006419:Heme Oxygenase (Decyclizing) / Q000235:genetics; D051547:Heme Oxygenase-1; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics; D058228:Islet Amyloid Polypeptide; D016173:Macrophage Colony-Stimulating Factor / Q000235:genetics; D008565:Membrane Proteins; D051379:Mice; D008810:Mice, Inbred C57BL; D009000:Monocytes / Q000166:cytology / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D011817:Rabbits; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000235:genetics / Q000378:metabolism*; D000685:Serum Amyloid A Protein / Q000378:metabolism*; D012835:Silver Nitrate / Q000378:metabolism / Q000494:pharmacology; D013154:Spleen / Q000378:metabolism / Q000473:pathology
D000682:Amyloid; D006023:Glycoproteins; D015850:Interleukin-6; D058228:Islet Amyloid Polypeptide; D008565:Membrane Proteins; D016328:NF-kappa B; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D000685:Serum Amyloid A Protein; C046748:amyloid enhancing factor; D016173:Macrophage Colony-Stimulating Factor; D012835:Silver Nitrate; C496541:HMOX1 protein, human; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1; C496542:Hmox1 protein, mouse