New Research In
Articles by Topic
- Agricultural Sciences
- Applied Biological Sciences
- Biophysics and Computational Biology
- Cell Biology
- Developmental Biology
- Environmental Sciences
- Immunology and Inflammation
- Medical Sciences
- Plant Biology
- Population Biology
- Psychological and Cognitive Sciences
- Sustainability Science
- Systems Biology
云南快乐十分前三走势:Targeting pericyte–endothelial cell crosstalk by circular RNA-cPWWP2A inhibition aggravates diabetes-induced microvascular dysfunction
This article requires a subscription to view the full text. If you have a subscription you may use the login form below to view the article. Access to this article can also be purchased.
The crosstalk between vascular endothelial cells (ECs) and pericytes in the microvascular is critical for vascular homeostasis and remodeling. However, the crosstalk between these two cells is often disrupted by diabetes, resulting in severe and even lethal vascular defects. Here, we show that diabetes-related stress up-regulates cPWWP2A expression in pericytes but not in ECs. Pericyte-derived cPWWP2A affects pericyte coverage and vascular integrity through interacting with miR-579 and its target genes, including angiopoietin 1/occludin/SIRT1. Our study thus reveals a critical role of cPWWP2A-mediated signaling in retinal microvascular dysfunction and implies potential therapeutic benefit with high-level expression of cPWWP2A or reduced miR-579 expression.
The crosstalk between vascular pericytes and endothelial cells (ECs) is critical for microvascular stabilization and remodeling; however, the crosstalk is often disrupted by diabetes, leading to severe and even lethal vascular damage. Circular RNAs are a class of endogenous RNAs that regulate several important physiological and pathological processes. Here we show that diabetes-related stress up-regulates cPWWP2A expression in pericytes but not in ECs. In vitro studies show that cPWWP2A directly regulates pericyte biology but indirectly regulates EC biology via exosomes carrying cPWWP2A. cPWWP2A acts as an endogenous miR-579 sponge to sequester and inhibit miR-579 activity, leading to increased expression of angiopoietin 1, occludin, and SIRT1. In vivo studies show that cPWWP2A overexpression or miR-579 inhibition alleviates diabetes mellitus-induced retinal vascular dysfunction. By contrast, inhibition of cPWWP2A-mediated signaling by silencing cPWWP2A or overexpressing miR-579 aggravates retinal vascular dysfunction. Collectively, this study unveils a mechanism by which pericytes and ECs communicate. Intervention of cPWWP2A or miR-579 expression may offer opportunities for treating diabetic microvascular complications.
?1C.L., H.-M.G., B.-H.L., and R.D. contributed equally to this work.
- ?2To whom correspondence may be addressed. Email: , , or .
Author contributions: B.Y. designed research; C.L., H.-M.G., B.-H.L., K.S., M.-D.Y., X.-M.L., J.Y., R.-M.Z., S.-J.Z., and B.Y. performed research; H.-M.G., X.C., and B.Y. contributed new reagents/analytic tools; C.L., R.D., Q.J., and C.Z. analyzed data; and B.Y. wrote the paper.
The authors declare no conflict of interest.
This article is a PNAS Direct Submission.
This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1814874116/-/DCSupplemental.
Published under the PNAS license.