AGE-modified collagens I and III induce keratinocyte terminal differentiation through AGE receptor CD36: epidermal-dermal interaction in acquired perforating dermatosis.
To clarify the molecular mechanism underlying the transepidermal extrusion of dermal collagen in acquired perforating dermatosis (APD) associated with diabetes mellitus and renal failure, we studied the interaction between advanced glycation end product (AGE)-modified extracellular matrix proteins and keratinocytes (KCs) in a cell culture system. The expression of involucrin (INV) and keratin 10 was significantly enhanced in normal human KCs grown on AGE-modified collagen I or III compared with cells grown on unmodified collagen I or III. Glycated collagens I and III preferentially induced the expression of AGE receptor CD36, but not of other AGE receptors. KCs induced to terminal differentiation demonstrated markedly elevated CD36 expression. Glycated collagen I- and III-induced INV expression was partially blocked by the anti-CD36 antibody (Ab). These substrates also induced epidermal matrix metalloproteinase 9 (MMP-9) expression. Lesional skin from APD patients reacted moderately or strongly with the anti-CD36 Ab as well as the anti-MMP-9 Ab in the epidermal cells surrounding the collagenous materials being eliminated. These results suggest that exposing KCs to AGE-modified interstitial collagen (types I and III) by scratching induces terminal differentiation of KCs via the AGE receptor (CD36), leading to the upward movement of KCs together with glycated collagen.
Department of Dermatology, National Defense Medical College, Tokorozawa, Saitama, Japan. dr20020@ndmc.ac.jp
Eita
E
Fujimoto
Takashi
T
Kobayashi
Norihiro
N
Fujimoto
Minoru
M
Akiyama
Shingo
S
Tajima
Ryoji
R
Nagai
D000328:Adult; D000368:Aged; D018955:CD36 Antigens / Q000096:biosynthesis* / Q000378:metabolism; D002454:Cell Differentiation; D024042:Collagen Type I / Q000378:metabolism*; D024061:Collagen Type III / Q000378:metabolism*; D020405:Dermis / Q000378:metabolism*; D004817:Epidermis / Q000378:metabolism*; D005260:Female; D017127:Glycation End Products, Advanced / Q000378:metabolism; D006801:Humans; D015603:Keratinocytes / Q000378:metabolism*; D007633:Keratins / Q000378:metabolism; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D008875:Middle Aged; D008954:Models, Biological; D012871:Skin Diseases / Q000378:metabolism*
D018955:CD36 Antigens; D024042:Collagen Type I; D024061:Collagen Type III; D017127:Glycation End Products, Advanced; D007633:Keratins; D020780:Matrix Metalloproteinase 9