Furong Gao, Mengwen Li, Lilin Zhu, Jiao Li, Jie Xu, Song Jia, Qingjian Ou, Caixia Jin, Haibin Tian, Juan Wang, Jingying Xu, Wei Xu, Guo-Tong Xu, Lixia Lu
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引用次数: 0
Abstract
Purpose: This study aimed to explore the impact of HSPA13 on epithelial-mesenchymal transition (EMT) in retinal pigment epithelial (RPE) cells and proliferative vitreoretinopathy (PVR) development, along with its associated molecular mechanisms.
Methods: HSPA13 expression was evaluated in epiretinal membranes (ERMs) from patients with PVR using immunohistochemistry. The effects of HSPA13 knockdown on TGFβ1-induced EMT in hESC-RPE cells were studied through quantitative PCR (qPCR), Western blot, and wound healing assays. Intracellular Ca2+ levels were measured using Fluo-8/AM incubation. A rat PVR model was induced by the intravitreal injection of RPE cells combined with platelet-rich plasma (PRP). RNA-seq was applied to study the molecular mechanism of HSPA13 knockdown-mediated EMT inhibition.
Results: HSPA13 was found in human ERMs and its expression increased with TGFβ1 treatment in hESC-RPE cells. Knockdown of HSPA13 inhibited TGFβ1-induced EMT and migration. In the PVR rat model, HSPA13 was expressed in the ERMs and its knockdown in RPE cells reduced the development of PVR. Consistent with these observations, RNA-seq showed a global suppression of TGFβ1-induced EMT and migration by shHSPA13 in RPE cells. Mechanistically, TGFβ1 treatment increased intracellular Ca2+ levels, leading to an upregulation of HSPA13 expression. Downregulation of HSPA13 hindered the phosphorylation of PI3K/Akt in TGFβ1-induced RPE cells.
Conclusions: Our study revealed the involvement of HSPA13 in PVR development, as well as in TGFβ1-induced EMT of RPE through the PI3K/Akt signaling pathway. Targeting HSPA13-related pathways involved in regulating EMT in RPE cells could serve as a novel therapeutic approach for patients with PVR.
期刊介绍:
Investigative Ophthalmology & Visual Science (IOVS), published as ready online, is a peer-reviewed academic journal of the Association for Research in Vision and Ophthalmology (ARVO). IOVS features original research, mostly pertaining to clinical and laboratory ophthalmology and vision research in general.