ORIGINAL RESEARCH article
Front. Cell Dev. Biol.
Sec. Molecular and Cellular Pathology
Loss of a primary cilia protein ARL13B promotes TGFβ-1 induced EMT of RPE in proliferative vitreoretinopathy via increasing Smad3 expression
Provisionally accepted
Wenjun Sui
Xinqi Ma
Yajun GongKairui QiuMiner YuanKeli Mao
Xiaobing Qian
Jieting Zeng
Yujie LiBingsheng Lou*
Xiaofeng Lin*
Xiaolai Zhou*- Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China
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Background: Proliferative vitreoretinopathy (PVR) is a major complication of rhegmatogenous retinal detachment. Epithelial-mesenchymal transition (EMT) of retinal pigment epithelial (RPE) plays a central role in PVR pathogenesis. This study aims to investigate the effect of ADP-ribosylation factor-like 13B (ARL13B) on RPE EMT in PVR. Methods: The expression of ARL13B in PVR specimens was analyzed by immunofluorescence (IF) staining. The effect of ARL13B on RPE EMT was assessed by IF staining and Western blot. The proliferation and migration of RPE were measured with EdU and transwell and scratch assays, respectively. The EMT-related transcriptome was analyzed by bulk RNAseq. An intravitreal injection mouse model of PVR was used to investigate the role of ARL13B in PVR formation. Results: Immunofluorescence revealed significantly reduced ARL13B levels in α-SMA-positive cells as compared with Pan-CK-positive cells in an epiretinal membrane derived from retinal tears. During EMT, TGFβ1 treatment remarkably reduced ARL13B expression and shortened the length of cilia in RPE cells. In line with this, ARL13B knockdown (KD) decreased the length of cilia and enhanced TGFβ1-induced EMT, evidenced by morphology change and a globally up-regulated EMT-related gene expression in RPEs. Moreover, ARL13B KD enhanced TGFβ1-induced RPE proliferation and migration. Consistently, ARL13B KD promoted PVR formation in vivo. Mechanistically, ARL13B KD enhanced TGFβ1 signaling by increasing the phosphorylation and expression of Smad3. Conclusions: This study demonstrated a crucial role of ARL13B on TGFβ1-induced RPE EMT, highlighting the importance of ARL13B in PVR formation.
Keywords: Proliferative vitreoretinopathy, Retinal pigment epithelial cells, Epithelial- mesenchymal transition, ARL13B, primary cilia
Received: 08 Jul 2025; Accepted: 10 Nov 2025.
Copyright: © 2025 Sui, Ma, Gong, Qiu, Yuan, Mao, Qian, Zeng, Li, Lou, Lin and Zhou. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Bingsheng Lou, loubsh3@mail.sysu.edu.cn
Xiaofeng Lin, linxiaof@mail.sysu.edu.cn
Xiaolai Zhou, zhouxiaolai@gzzoc.com
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