RRC ID 61629
Author Kubo Y, Ishikawa K, Mori K, Kobayashi Y, Nakama T, Arima M, Nakao S, Hisatomi T, Haruta M, Sonoda KH, Yoshida S.
Title Periostin and tenascin-C interaction promotes angiogenesis in ischemic proliferative retinopathy.
Journal Sci Rep
Abstract Ischemic proliferative retinopathy (IPR), such as proliferative diabetic retinopathy (PDR), retinal vein occlusion and retinopathy of prematurity is a major cause of vision loss. Our previous studies demonstrated that periostin (PN) and tenascin-C (TNC) are involved in the pathogenesis of IPR. However, the interactive role of PN and TNC in angiogenesis associated with IPR remain unknown. We found significant correlation between concentrations of PN and TNC in PDR vitreous humor. mRNA and protein expression of PN and TNC were found in pre-retinal fibrovascular membranes excised from PDR patients. Interleukin-13 (IL-13) promoted mRNA and protein expression of PN and TNC, and co-immunoprecipitation assay revealed binding between PN and TNC in human microvascular endothelial cells (HRECs). IL-13 promoted angiogenic functions of HRECs. Single inhibition of PN or TNC and their dual inhibition by siRNA suppressed the up-regulated angiogenic functions. Pathological pre-retinal neovessels of oxygen-induced retinopathy (OIR) mice were attenuated in PN knock-out, TNC knock-out and dual knock-out mice compared to wild-type mice. Both in vitro and in vivo, PN inhibition had a stronger inhibitory effect on angiogenesis compared to TNC inhibition, and had a similar effect to dual inhibition of PN and TNC. Furthermore, PN knock-out mice showed scant TNC expression in pre-retinal neovessels of OIR retinas. Our findings suggest that interaction of PN and TNC facilitates pre-retinal angiogenesis, and PN is an effective therapeutic target for IPR such as PDR.
Volume 10(1)
Pages 9299
Published 2020-6-9
DOI 10.1038/s41598-020-66278-1
PII 10.1038/s41598-020-66278-1
PMID 32518264
PMC PMC7283227
MeSH Aged Animals Cell Adhesion Molecules / genetics Cell Adhesion Molecules / metabolism* Cells, Cultured Diabetic Retinopathy / pathology* Endothelial Cells / metabolism Female Humans Interleukin-13 / metabolism Male Mice Mice, Inbred C57BL Mice, Knockout Middle Aged Neovascularization, Pathologic / pathology* Retinal Vessels / growth & development* Tenascin / genetics Tenascin / metabolism* Vitreoretinopathy, Proliferative / pathology* Vitreous Body / metabolism
IF 3.998
Mice RBRC00169