Pigment epithelium-derived factor (PEDF) promotes growth of pericytes through autocrine production of platelet-derived growth factor-B.
Microvessels are composed of two types of cells, endothelial cells and pericytes. Pericyte loss or dysfunction participates in various types of disorders, including diabetic retinopathy. Recently, decreased levels of pigment epithelium-derived factor (PEDF) in the eye have been found to predict progression of diabetic retinopathy. However, the effect of PEDF on pericyte growth remains to be unknown. In this study, we investigated whether or how PEDF could stimulate proliferation of cultured retinal pericytes. PEDF stimulated DNA synthesis in pericytes in a dose-dependent manner. PEDF up-regulated pericyte mRNA levels of platelet-derived growth factor-B (PDGF-B). Down-regulation of PDGF-B gene expression by small interfering RNAs completely inhibited the PEDF-induced DNA synthesis in pericytes. Furthermore, PEDF increased protein kinase C (PKC) activity in pericytes and staurosporine, a potent cell-permeable inhibitor of PKC, completely blocked the PDGF-B gene induction and subsequent increase in DNA synthesis in PEDF-exposed pericytes. These results demonstrate that PEDF promotes the growth of cultured pericytes possibly through autocrine production of PDGF-B via PKC activation. Our present study suggests that PEDF could act as a mitogen or survival factor for pericytes, thereby being involved in the maintenance of retinal microvascular homeostasis.
Yamagishi
Sho-Ichi
S
Department of Internal Medicine III, Kurume University School of Medicine, 67 Asahi-machi, Kurume 830-0011, Japan. shoichi@med.kurume-u.ac.jp
Nakamura
Kazuo
K
Takenaka
Katsuhiko
K
Matsui
Takanori
T
Jinnouchi
Yuko
Y
Imaizumi
Tsutomu
T
D000818:Animals; D019898:Autocrine Communication / Q000187:drug effects*; D001483:Base Sequence; D001792:Blood Platelets / Q000737:chemistry*; D002417:Cattle; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005136:Eye Proteins / Q000302:isolation & purification / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects*; D008969:Molecular Sequence Data; D009414:Nerve Growth Factors / Q000302:isolation & purification / Q000494:pharmacology*; D020286:Pericytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D010982:Platelet-Derived Growth Factor / Q000737:chemistry / Q000494:pharmacology*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000494:pharmacology; D012160:Retina / Q000166:cytology; D012689:Sequence Homology, Nucleic Acid; D015843:Serpins / Q000302:isolation & purification / Q000494:pharmacology*; D019311:Staurosporine / Q000494:pharmacology; D015533:Transcriptional Activation; D000099174:Pigment Epithelium-Derived Factor
D004247:DNA; D004791:Enzyme Inhibitors; D005136:Eye Proteins; D009414:Nerve Growth Factors; D010982:Platelet-Derived Growth Factor; D011493:Protein Kinase C; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D015843:Serpins; D019311:Staurosporine; D000099174:Pigment Epithelium-Derived Factor