CTGF Contributes to the Development of Posterior Capsule Opacification: an <i>in vitro</i> and <i>in vivo</i> study

Ma, Bo; Jing, Ruihua; Liu, Jie; Yang, Lan; Li, Jingming; Li, Qin; Cui, Liangliang; Pei, Cheng

doi:10.7150/ijbs.23946

Cited by 20 publications

(16 citation statements)

References 48 publications

(39 reference statements)

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“…Ten eyes of five pigs were obtained from an abattoir. The porn capsular bag model was created as described in our previous study [25]. The capsular bags, which were treated with gremlin at 200 μg/L or control medium, were incubated in MEM medium (CM10010, M&C Gene Technology Ltd., China) for 14 days in an incubator of 5% CO 2 at 38°C.…”

Section: Preparation Of Capsular Bag Modelmentioning

confidence: 99%

“…The transwell migration assay and Wound healing assay were performed to identify and evaluate the chemical cues of gremlin on cell migration as described in our previous study [25]. Briefly, in the transwell assay, 10 4 cells were seeded in the upper chamber and serumfree medium with or without containing 200 μg/ L gremlin was placed in the bottom compartment.…”

Section: Wound Healing Assay and Transwell® Migration Assaymentioning

confidence: 99%

“…Therefore, we hypothesized that targeting gremlin could delay the onset of PCO or alleviate its symptoms. To test this hypothesis, we enrolled in an in vivo rat PCO model which described in detail in our previous study [25]. In short, after rats were anesthetized using sodium pentobarbital and pupils diluted, viscoelastic was injected to form the anterior chamber from the 11point corneal 2.0 mm cut.…”

Section: Specific Silencing Of Gremlin Inhibits Pco Development In Ratsmentioning

confidence: 99%

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Gremlin is a potential target for posterior capsular opacification

Jing

Liu

et al. 2019

Cell Cycle

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Objective: The present study was conducted to determine the role of gremlin during the development of posterior capsular opacification (PCO) via in vitro and in vivo experiments. Methods: The activation, roles and relationships of the BMPs/Smad1/5, MAPK, FAK and AKT signaling pathways in human lens epithelial cells (HLECs) after gremlin induction were detected by western blotting and real-time PCR. Wound-healing, transwell, capsular bag models and rat PCO models assays were used to test the effects of gremlin on HLECs' migration, proliferation, EMT-specific protein α-smooth muscle actin(α-SMA)and development of PCO in rats. Results: Our data showed that knockdown of the gremlin inhibited the development of PCO and reduced expression of α-SMA in rats. While gremlin did not alter the migration of HLECs, it increased the expression of pERK and p-AKT. Knockout of Smad2 or Smad3 inhibited the expression of pERK and p-AKT proteins induced by gremlin. Gremlin also reduced BMP4induced expression of the p-Smad1/5 protein. Finally, knockout of Smad1/5 increased gremlininduced expression of α-SMA, fibronectin and type I collagen (COL-1) in HLECs. Conclusion: These results suggested that gremlin contributed to the development of PCO by promoting LEC proliferation, activation of TGF-β/Smad, ERK and AKT signaling and inhibition of BMPs/Smad1/5 signaling. Furthermore, inhibiting gremlin effectively impaired both PCO development in rats and EMT in the lens capsule. Thus, our data suggest that gremlin might be a potential target for PCO.

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Section: Preparation Of Capsular Bag Modelmentioning

confidence: 99%

Section: Wound Healing Assay and Transwell® Migration Assaymentioning

confidence: 99%

Section: Specific Silencing Of Gremlin Inhibits Pco Development In Ratsmentioning

confidence: 99%

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Gremlin is a potential target for posterior capsular opacification

Jing

Liu

et al. 2019

Cell Cycle

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“…Previous studies demonstrated that TGF-β2 played an essential role in the formation of PCO via the canonical TGF-β/Smad signaling pathway, as well as via non-canonical signaling [ 20 , 46 ]. Activation of the ERK signaling pathway was involved in cell carcinogenesis, cancer cell metastasis, and a series of fibrotic diseases, including PCO [ 26 , 47 , 48 ]. Our study revealed the critical role of the ERK signaling pathway in the TGF-β2-induced EMT of human LECs.…”

Section: Discussionmentioning

confidence: 99%

Drug-eluting intraocular lens with sustained bromfenac release for conquering posterior capsular opacification

Zhang

Lai

et al. 2022

Bioactive Materials

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Cataract is the leading cause of visual impairment, and posterior capsular opacification (PCO) is the most common long-term complication of modern cataract surgery, which can cause severe visual impairment after surgery. The proliferation, migration, and epithelial-mesenchymal transition (EMT) of residual lens epithelial cells (LECs) stimulated by growth factors and cytokines, are the key pathological mechanisms involved in the development of PCO. This study demonstrated that non-steroidal anti-inflammatory drug (NSAID), bromfenac, was capable of effectively inhibiting cell migration, overexpression of EMT markers, such as fibronectin (FN), matrix metalloproteinase 2 (MMP2), α-smooth muscle actin (α-SMA), and transcription factor Snail, and extracellular signal-regulated kinase (ERK)/glycogen synthase kinase-3β (GSK-3β) signaling induced by transforming growth factor-β2 (TGF-β2) in vitro . The inhibitory effect of bromfenac on TGF-β2-induced EMT was also verified on a primary lens epithelial cell model using human anterior capsules. Furthermore, based on ultrasonic spray technology, we developed a drug-eluting intraocular lens (IOL) using poly (lactic-co-glycolic acid) (PLGA) with sustained bromfenac release ability for the prevention of PCO development. In the rabbit models of cataract surgery, bromfenac-eluting IOL exhibited remarkable PCO prevention and inflammation suppression effects with excellent biocompatibility. In conclusion, bromfenac can inhibit TGF-β2-induced cell migration and the EMT of LECs via ERK/GSK-3β/Snail signaling. The present study offers a novel approach for preventing PCO through PLGA-based drug sustained-release IOLs.

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“…Wound healing and Transwell ® migration assay were performed as described in our previous study (Ma, Jing, et al., ). The cells were in serum‐free medium containing 10 μg/L IL‐2 with or without WP1066 (S2796; Selleck) or BAY 11‐7082 (S2913; Selleck).…”

Section: Methodsmentioning

confidence: 99%

Interleukin‐2 induces extracellular matrix synthesis and TGF‐β2 expression in retinal pigment epithelial cells

Jing

Wen

et al. 2019

Dev Growth Differ

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Macular fibrosis is a vital obstacle of vision acuity improvement of age‐related macular degeneration patients. This study was to investigate the effects of interleukin 2 (IL‐2) on epithelial‐mesenchymal transition (EMT), extracellular matrix (ECM) synthesis and transforming growth factor β2 (TGF‐β2) expression in retinal pigment epithelial (RPE) cells. 10 μg/L IL‐2 was used to induce fibrosis in RPE cells for various times. Western blot was used to detect the EMT marker α‐smooth muscle actin (α‐SMA), ECM markers fibronectin (Fn) and type 1 collagen (COL‐1), TGF‐β2, and the activation of the JAK/STAT3 and NF‐κB signaling pathway. Furthermore, JAK/STAT3 and NF‐κB signaling pathways were specifically blocked by WP1066 or BAY11‐7082, respectively, and the expression of α‐SMA, COL‐1, Fn and TGF‐β2 protein were detected. Wound healing and Transwell assays were used to measure cell migration ability of IL‐2 with or without WP1066 or BAY11‐7082. After induction of IL‐2, the expressions of Fn, COL‐1, TGF‐β2 protein were significantly increased, and this effect was correlated with IL‐2 treatment duration, while α‐SMA protein expression did not change significantly. Both WP1066 and BAY11‐7082 could effectively downregulate the expression of Fn, COL‐1 and TGF‐β2 induced by IL‐2. What's more, both NF‐κB and JAK/STAT3 inhibitors could suppress the activation of the other signaling pathway. Additionally, JAK/STAT3 inhibitor WP1066 and NF‐κB inhibitor BAY 11‐7082 could obviously decrease RPE cells migration capability induced by IL‐2. IL‐2 promotes cell migration, ECM synthesis and TGF‐β2 expression in RPE cells via JAK/STAT3 and NF‐κB signaling pathways, which may play an important role in proliferative vitreoretinopathy.

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CTGF Contributes to the Development of Posterior Capsule Opacification: an in vitro and in vivo study

Cited by 20 publications

References 48 publications

Gremlin is a potential target for posterior capsular opacification

Gremlin is a potential target for posterior capsular opacification

Drug-eluting intraocular lens with sustained bromfenac release for conquering posterior capsular opacification

Interleukin‐2 induces extracellular matrix synthesis and TGF‐β2 expression in retinal pigment epithelial cells

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