MicroRNA-204-5p Regulates Epithelial-to-Mesenchymal Transition during Human Posterior Capsule Opacification by Targeting SMAD4

Wang, Ye; Li, Wenfeng; Zang, Xinjie; Chen, Nan; Liu, Ting; Tsonis, Panagiotis A.; Huang, Yusen

doi:10.1167/iovs.12-10904

Cited by 83 publications

(60 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In contrast to the above results, the mRNA levels of miR204, miR184, TGFβR2, TGFβR3, and BMP4, which have been previously shown to be downregulated by TGFβ2 in HLE cells (Dawes et al ., 2007; Wang et al ., 2013), were expectedly downregulated by the TGFβ2 treatment (Fig. 4).…”

Section: Resultsmentioning

confidence: 85%

“…Numerous studies have implicated the TGFβ/Smad signaling pathway in PCO (Saika et al ., 2004; Wormstone et al ., 2004). αSMA, MMP2, CTGF, integrin αV, integrin α5, integrin β1, miR4279, and miR1469 have been shown to be upregulated by TGFβ2 during the EMT of HLE cells (Dawes et al ., 2007; Wang et al ., 2013; Mamuya et al ., 2014). Therefore, we measured the mRNA levels of these proteins by qPCR.…”

Section: Resultsmentioning

confidence: 99%

“…In addition, aberration in integrin‐mediated cell anchoring has also been implicated in lens epithelial cell EMT (Mamuya et al ., 2014). Recent studies have also shown a role for aldose reductase, MMP, microRNA, and histone deacetylases in lens epithelial cell EMT (Yadav et al ., 2009; Wang et al ., 2013; Korol et al ., 2014; Xie et al ., 2014). …”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

AGEs in human lens capsule promote the TGFβ2‐mediated EMT of lens epithelial cells: implications for age‐associated fibrosis

et al. 2016

View full text Add to dashboard Cite

SummaryProteins in basement membrane (BM) are long‐lived and accumulate chemical modifications during aging; advanced glycation endproduct (AGE) formation is one such modification. The human lens capsule is a BM secreted by lens epithelial cells. In this study, we have investigated the effect of aging and cataracts on the AGE levels in the human lens capsule and determined their role in the epithelial‐to‐mesenchymal transition (EMT) of lens epithelial cells. EMT occurs during posterior capsule opacification (PCO), also known as secondary cataract formation. We found age‐dependent increases in several AGEs and significantly higher levels in cataractous lens capsules than in normal lens capsules measured by LC‐MS/MS. The TGFβ2‐mediated upregulation of the mRNA levels (by qPCR) of EMT‐associated proteins was significantly enhanced in cells cultured on AGE‐modified BM and human lens capsule compared with those on unmodified proteins. Such responses were also observed for TGFβ1. In the human capsular bag model of PCO, the AGE content of the capsule proteins was correlated with the synthesis of TGFβ2‐mediated α‐smooth muscle actin (αSMA). Taken together, our data imply that AGEs in the lens capsule promote the TGFβ2‐mediated fibrosis of lens epithelial cells during PCO and suggest that AGEs in BMs could have a broader role in aging and diabetes‐associated fibrosis.

show abstract

Section: Resultsmentioning

confidence: 85%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

AGEs in human lens capsule promote the TGFβ2‐mediated EMT of lens epithelial cells: implications for age‐associated fibrosis

et al. 2016

View full text Add to dashboard Cite

show abstract

“…Interestingly, another study in our lab found that the expression of miR-204-5p was downregulated 66.8-fold in human posterior capsule opacification (PCO) tissues compared to those in the normal attached lens epithelial cells (LECs). 15 These data uncovered the multiexpression pattern of miR-204-5p in the eye, suggesting miR-204-5p may be one of the key miRNAs in different diseases of the eye. We then investigated the role of miR-204-5p in regulating SIRT1 in diabetic keratopathy.…”

mentioning

confidence: 82%

MicroRNA-204-5p-Mediated Regulation of SIRT1 Contributes to the Delay of Epithelial Cell Cycle Traversal in Diabetic Corneas

Gao

Wang

Zhao

et al. 2015

Investigative Ophthalmology & Visual Science

View full text Add to dashboard Cite

show abstract

“…By targeting SMAD4 , miR-204-5p inhibits EMT in the LECs of a human donor capsular bag model in vitro. Development of PCO involves miR-204-5p and SMAD4 in the EMT, and hence miR-204-5p serves as a novel target for therapeutic intervention in PCO [25]. In addition to miR-204-5p, miR-26b was also found to target SMAD4 mRNA.…”

Section: Mirnas and Eye Disordersmentioning

confidence: 99%

Micro-RNAs and Their Roles in Eye Disorders

Raghunath¹,

Perumal²

2015

Ophthalmic Res

View full text Add to dashboard Cite

Micro-RNAs (miRNAs) are members of the family of noncoding RNA molecules that regulate gene expression by translational repression and mRNA degradation. Initial identification of miRNAs revealed them only as developmental regulators; later, their radiated roles in various cellular processes have been established. They regulate several pathways, including developmental timing, hematopoiesis, organogenesis, apoptosis, cell differentiation and proliferation. Their roles in eye disorders are being explored by biologists around the world. Eye physiology requires the perfect orchestration of all the regulatory networks; any defect in any of the networks leads to eye disorders. The dysregulation of miRNA expression has been reported in many eye disorders, which paves the way for new therapeutics. This review summarizes the biogenesis of miRNAs and their role in eye disorders. miRNA studies also have implications for the understanding of various complex metabolic pathways leading to disorders of the eye. The ultimate understanding leads to potential opportunities in evaluating miRNAs as molecular biomarkers, prognostic tools, diagnostic tools and therapeutic agents for eye disorders.

show abstract

MicroRNA-204-5p Regulates Epithelial-to-Mesenchymal Transition during Human Posterior Capsule Opacification by Targeting SMAD4

Abstract: Our data provide firm evidence of a role for miR-204-5p in the direct regulation of EMT through its targeting of SMAD4 and, consequently, TGF-β signaling. Because of its ability to repress the EMT, miR-204-5p may be a novel target for PCO therapeutic intervention.

Cited by 83 publications

References 35 publications

AGEs in human lens capsule promote the TGFβ2‐mediated EMT of lens epithelial cells: implications for age‐associated fibrosis

AGEs in human lens capsule promote the TGFβ2‐mediated EMT of lens epithelial cells: implications for age‐associated fibrosis

MicroRNA-204-5p-Mediated Regulation of SIRT1 Contributes to the Delay of Epithelial Cell Cycle Traversal in Diabetic Corneas

Micro-RNAs and Their Roles in Eye Disorders

Contact Info

Product

Resources

About