Periostin, discovered by nano-flow liquid chromatography and mass spectrometry, is a novel marker of diabetic retinopathy.
Diabetes can lead to serious microvascular complications including proliferative diabetic retinopathy (PDR), the leading cause of blindness in adults. Recent studies using gene array technology have attempted to apply a hypothesis-generating approach to elucidate the pathogenesis of PDR, but these studies rely on mRNA differences, which may or may not be related to significant biological processes. To better understand the basic mechanisms of PDR and to identify potential new biomarkers, we performed shotgun liquid chromatography (LC)/tandem mass spectrometry (MS/MS) analysis on pooled protein extracts from neovascular membranes obtained from PDR specimens and compared the results with those from non-vascular epiretinal membrane (ERM) specimens. We detected 226 distinct proteins in neovascular membranes and 154 in ERM. Among these proteins, 102 were specific to neovascular membranes and 30 were specific to ERM. We identified a candidate marker, periostin, as well as several known PDR markers such as pigment epithelium-derived factor (PEDF). We then performed RT-PCR using these markers. The expression of periostin was significantly up-regulated in proliferative membrane specimens. Periostin induces cell attachment and spreading and plays a role in cell adhesion. Proteomic analysis by LC/MS/MS, which permits accurate quantitative comparison, was useful in identifying new candidates such as periostin potentially involved in the pathogenesis of PDR.
Takada
Michiya
M
Division of Diabetes, Metabolism and Endocrinology, Department of Internal Medicine, Showa University School of Medicine, Tokyo, Japan.
Ban
Yoshiyuki
Y
Yamamoto
Gou
G
Ueda
Toshihiko
T
Saito
Yuta
Y
Nishimura
Eiichi
E
Fujisawa
Kunimi
K
Koide
Ryohei
R
Mizutani
Masakazu
M
Kozawa
Tadahiko
T
Shiraishi
Yuji
Y
Bando
Yasuhiko
Y
Tachikawa
Tetsuhiko
T
Hirano
Tsutomu
T
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000032:analysis / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D002853:Chromatography, Liquid / Q000379:methods*; D003930:Diabetic Retinopathy / Q000378:metabolism*; D019773:Epiretinal Membrane / Q000378:metabolism; D005136:Eye Proteins / Q000032:analysis / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009414:Nerve Growth Factors / Q000032:analysis / Q000378:metabolism; D015843:Serpins / Q000032:analysis / Q000378:metabolism; D053719:Tandem Mass Spectrometry / Q000379:methods*; D000099174:Pigment Epithelium-Derived Factor
D015415:Biomarkers; D015815:Cell Adhesion Molecules; D005136:Eye Proteins; D009414:Nerve Growth Factors; D015843:Serpins; D000099174:Pigment Epithelium-Derived Factor; C512835:POSTN protein, human