Investigative ophthalmology & visual science · 2026
The Matricellular Protein CCN1 Induces Corneal Stromal Cells Senescence and Inflammation to Trigger Extracellular Matrix Remodeling in Keratoconus.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Zhang Lei, Wei Chaoqun, Li Yifei, Shi Jiahao, Chi Yuqi, Zhang Yadi, Bao Qingdong, Li Wenlong, Liu Xiaoxue, Gao Hua
Аннотация
PURPOSE: Keratoconus (KC) is a multifactorial corneal degenerative disorder characterized by reduced extracellular matrix (ECM) and cellular content. This study investigates the role and mechanism of cellular communication network factor 1 (CCN1) in KC progression.
METHODS: The expression of CCN1 was first examined in clinical samples using Western blot and immunofluorescence staining. A CCN1 overexpression cell model (OE CCN1) was then established by transfecting primary corneal stromal cells with CCN1 OE plasmids, and RNA sequencing was performed to identify downstream molecular pathways regulated by CCN1. Subsequently, multiple methodologies, including SA‑β‑Gal staining, enzyme‑linked immunosorbent assay (ELISA), qRT‑PCR, Western blot, immunofluorescence staining, flow cytometry, and transmission electron microscopy (TEM), were used to systematically evaluate the role of CCN1 in KC samples and corneal stromal cells.
RESULTS: CCN1 expression was significantly elevated in patients with KC. CCN1 OE markedly upregulated senescence and inflammatory pathways, increased expression of γH2AX, p16, p21, p53, and senescence-associated secretory phenotype (SASP) molecules. Additionally, CCN1 led to reactive oxygen species (ROS) accumulation, G2/M phase cell cycle arrest, enhanced apoptosis, lysosomal dysfunction, and matrix metalloproteinases (MMPs) OE, collectively contributing to ECM remodeling.
CONCLUSIONS: CCN1 plays a critical role in promoting corneal degeneration in KC and may serve as a potential therapeutic target to halt or slow disease progression.
METHODS: The expression of CCN1 was first examined in clinical samples using Western blot and immunofluorescence staining. A CCN1 overexpression cell model (OE CCN1) was then established by transfecting primary corneal stromal cells with CCN1 OE plasmids, and RNA sequencing was performed to identify downstream molecular pathways regulated by CCN1. Subsequently, multiple methodologies, including SA‑β‑Gal staining, enzyme‑linked immunosorbent assay (ELISA), qRT‑PCR, Western blot, immunofluorescence staining, flow cytometry, and transmission electron microscopy (TEM), were used to systematically evaluate the role of CCN1 in KC samples and corneal stromal cells.
RESULTS: CCN1 expression was significantly elevated in patients with KC. CCN1 OE markedly upregulated senescence and inflammatory pathways, increased expression of γH2AX, p16, p21, p53, and senescence-associated secretory phenotype (SASP) molecules. Additionally, CCN1 led to reactive oxygen species (ROS) accumulation, G2/M phase cell cycle arrest, enhanced apoptosis, lysosomal dysfunction, and matrix metalloproteinases (MMPs) OE, collectively contributing to ECM remodeling.
CONCLUSIONS: CCN1 plays a critical role in promoting corneal degeneration in KC and may serve as a potential therapeutic target to halt or slow disease progression.