circZNF532 promotes endothelial-to-mesenchymal transition in diabetic retinopathy by recruiting TAF15 to stabilize PIK3CD

Endothelial-to-mesenchymal transition (EndMT) is a pivotal event in diabetic retinopathy (DR). This study explored the role of circRNA zinc finger protein 532 (circZNF532) in regulating EndMT in DR progression. Human retinal microvascular endothelial cells (HRMECs) were exposed to high glucose (HG)...

Full description

Saved in:
Bibliographic Details
Main Authors: Xiao-Lin Fu, Fu-Tao He, Mo-Han Li, Chun-Yan Fu, Jian-Zhi Chen
Format: Article
Language:English
Published: The Japan Endocrine Society 2024-07-01
Series:Endocrine Journal
Subjects:
Online Access:https://www.jstage.jst.go.jp/article/endocrj/71/7/71_EJ23-0683/_html/-char/en
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1832591938925101056
author Xiao-Lin Fu
Fu-Tao He
Mo-Han Li
Chun-Yan Fu
Jian-Zhi Chen
author_facet Xiao-Lin Fu
Fu-Tao He
Mo-Han Li
Chun-Yan Fu
Jian-Zhi Chen
author_sort Xiao-Lin Fu
collection DOAJ
description Endothelial-to-mesenchymal transition (EndMT) is a pivotal event in diabetic retinopathy (DR). This study explored the role of circRNA zinc finger protein 532 (circZNF532) in regulating EndMT in DR progression. Human retinal microvascular endothelial cells (HRMECs) were exposed to high glucose (HG) to induce the DR cell model. Actinomycin D-treated HRMECs were used to confirm the mRNA stability of phosphoinositide-3 kinase catalytic subunit δ (PIK3CD). The interaction between TATA-box-binding protein-associated factor 15 (TAF15) and circZNF532/PIK3CD was subsequently analyzed using RNA immunoprecipitation (RIP), RNA pull-down. It was found that HG treatment accelerated EndMT process, facilitated cell migration and angiogenesis, and enhanced PIK3CD and p-AKT levels in HRMECs, whereas si-circZNF532 transfection neutralized these effects. Further data showed that circZNF532 recruited TAF15 to stabilize PIK3CD, thus elevating PIK3CD expression. Following rescue experiments suggested that PIK3CD overexpression partially negated the inhibitory effect of circZNF532 silencing on EndMT, migration, and angiogenesis of HG-treated HRMECs. In conclusion, our results suggest that circZNF532 recruits TAF15 to stabilize PIK3CD, thereby facilitating EndMT in DR.
format Article
id doaj-art-d98e612c185347c7ace909af21835809
institution Kabale University
issn 1348-4540
language English
publishDate 2024-07-01
publisher The Japan Endocrine Society
record_format Article
series Endocrine Journal
spelling doaj-art-d98e612c185347c7ace909af218358092025-01-22T05:12:18ZengThe Japan Endocrine SocietyEndocrine Journal1348-45402024-07-0171767568610.1507/endocrj.EJ23-0683endocrjcircZNF532 promotes endothelial-to-mesenchymal transition in diabetic retinopathy by recruiting TAF15 to stabilize PIK3CDXiao-Lin Fu0Fu-Tao He1Mo-Han Li2Chun-Yan Fu3Jian-Zhi Chen4Department of Ophthalmology, Hainan West Central Hospital, Danzhou 571700, Hainan Province, P.R. ChinaDepartment of Ophthalmology, Hainan West Central Hospital, Danzhou 571700, Hainan Province, P.R. ChinaDepartment of Ophthalmology, Hainan West Central Hospital, Danzhou 571700, Hainan Province, P.R. ChinaDepartment of Ophthalmology, Hainan West Central Hospital, Danzhou 571700, Hainan Province, P.R. ChinaDepartment of Ophthalmology, Hainan West Central Hospital, Danzhou 571700, Hainan Province, P.R. ChinaEndothelial-to-mesenchymal transition (EndMT) is a pivotal event in diabetic retinopathy (DR). This study explored the role of circRNA zinc finger protein 532 (circZNF532) in regulating EndMT in DR progression. Human retinal microvascular endothelial cells (HRMECs) were exposed to high glucose (HG) to induce the DR cell model. Actinomycin D-treated HRMECs were used to confirm the mRNA stability of phosphoinositide-3 kinase catalytic subunit δ (PIK3CD). The interaction between TATA-box-binding protein-associated factor 15 (TAF15) and circZNF532/PIK3CD was subsequently analyzed using RNA immunoprecipitation (RIP), RNA pull-down. It was found that HG treatment accelerated EndMT process, facilitated cell migration and angiogenesis, and enhanced PIK3CD and p-AKT levels in HRMECs, whereas si-circZNF532 transfection neutralized these effects. Further data showed that circZNF532 recruited TAF15 to stabilize PIK3CD, thus elevating PIK3CD expression. Following rescue experiments suggested that PIK3CD overexpression partially negated the inhibitory effect of circZNF532 silencing on EndMT, migration, and angiogenesis of HG-treated HRMECs. In conclusion, our results suggest that circZNF532 recruits TAF15 to stabilize PIK3CD, thereby facilitating EndMT in DR.https://www.jstage.jst.go.jp/article/endocrj/71/7/71_EJ23-0683/_html/-char/endiabetic retinopathy (dr)human retinal microvascular endothelial cells (hrmecs)endothelial-to-mesenchymal transition (endmt)circrna zinc finger protein 532 (circznf532)phosphoinositide-3 kinase catalytic subunit δ (pik3cd)
spellingShingle Xiao-Lin Fu
Fu-Tao He
Mo-Han Li
Chun-Yan Fu
Jian-Zhi Chen
circZNF532 promotes endothelial-to-mesenchymal transition in diabetic retinopathy by recruiting TAF15 to stabilize PIK3CD
Endocrine Journal
diabetic retinopathy (dr)
human retinal microvascular endothelial cells (hrmecs)
endothelial-to-mesenchymal transition (endmt)
circrna zinc finger protein 532 (circznf532)
phosphoinositide-3 kinase catalytic subunit δ (pik3cd)
title circZNF532 promotes endothelial-to-mesenchymal transition in diabetic retinopathy by recruiting TAF15 to stabilize PIK3CD
title_full circZNF532 promotes endothelial-to-mesenchymal transition in diabetic retinopathy by recruiting TAF15 to stabilize PIK3CD
title_fullStr circZNF532 promotes endothelial-to-mesenchymal transition in diabetic retinopathy by recruiting TAF15 to stabilize PIK3CD
title_full_unstemmed circZNF532 promotes endothelial-to-mesenchymal transition in diabetic retinopathy by recruiting TAF15 to stabilize PIK3CD
title_short circZNF532 promotes endothelial-to-mesenchymal transition in diabetic retinopathy by recruiting TAF15 to stabilize PIK3CD
title_sort circznf532 promotes endothelial to mesenchymal transition in diabetic retinopathy by recruiting taf15 to stabilize pik3cd
topic diabetic retinopathy (dr)
human retinal microvascular endothelial cells (hrmecs)
endothelial-to-mesenchymal transition (endmt)
circrna zinc finger protein 532 (circznf532)
phosphoinositide-3 kinase catalytic subunit δ (pik3cd)
url https://www.jstage.jst.go.jp/article/endocrj/71/7/71_EJ23-0683/_html/-char/en
work_keys_str_mv AT xiaolinfu circznf532promotesendothelialtomesenchymaltransitionindiabeticretinopathybyrecruitingtaf15tostabilizepik3cd
AT futaohe circznf532promotesendothelialtomesenchymaltransitionindiabeticretinopathybyrecruitingtaf15tostabilizepik3cd
AT mohanli circznf532promotesendothelialtomesenchymaltransitionindiabeticretinopathybyrecruitingtaf15tostabilizepik3cd
AT chunyanfu circznf532promotesendothelialtomesenchymaltransitionindiabeticretinopathybyrecruitingtaf15tostabilizepik3cd
AT jianzhichen circznf532promotesendothelialtomesenchymaltransitionindiabeticretinopathybyrecruitingtaf15tostabilizepik3cd