scholarly journals Role of Decorin in Posterior Capsule Opacification and Eye Lens Development

Cells ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 863
Author(s):  
Shinsuke Shibata ◽  
Naoko Shibata ◽  
Satoshi Ohtsuka ◽  
Yasuo Yoshitomi ◽  
Etsuko Kiyokawa ◽  
...  
Keyword(s):  
Growth Factor ◽  
Transforming Growth Factor ◽  
Epithelial Mesenchymal Transition ◽  
Smooth Muscle Actin ◽  
Expression Patterns ◽  
Posterior Capsule Opacification ◽  
Posterior Capsule ◽  
Mesenchymal Transition ◽  
Mouse Lens

Decorin (DCN) is involved in a variety of physiological and pathological processes. Epithelial-mesenchymal transition (EMT) of lens epithelial cells (LECs) has been proposed as a major cause for the development of posterior capsule opacification (PCO) after cataract surgery. We investigated the plausible target gene(s) that suppress PCO. The expression of Dcn was significantly upregulated in rat PCO tissues compared to that observed in the control using a microarray-based approach. LECs treated with fibroblast growth factor (FGF) 2 displayed an enhanced level of DCN expression, while LECs treated with transforming growth factor (TGF)β-2 showed a decrease in DCN expression. The expression of tropomyosin 1 (Tpm1), a marker of lens EMT increased after the addition of TGFβ-2 in human LEC; however, upregulation of Tpm1 mRNA or protein expression was reduced in human LECs overexpressing human DCN (hDCN). No phenotypic changes were observed in the lenses of 8- and 48-week-old transgenic mice for lens-specific hDCN (hDCN-Tg). Injury-induced EMT of the mouse lens, and the expression patterns of α smooth muscle actin, were attenuated in hDCN-Tg mice lenses. Overexpression of DCN inhibited the TGFβ-2-induced upregulation of Tpm1 and EMT observed during wound healing of the lens, but it did not affect mouse lens morphology until 48 weeks of age. Our findings demonstrate that DCN plays a significant role in regulating EMT formation of LECs and PCO, and suggest that for therapeutic intervention, maintenance of physiological expression of DCN is essential to attenuate EMT progression and PCO formation.

scholarly journals TGF-β and the Smad Signaling Pathway Support Transcriptomic Reprogramming during Epithelial-Mesenchymal Cell Transition

2005 ◽  
Vol 16 (4) ◽  
pp. 1987-2002 ◽  
Author(s):  
Ulrich Valcourt ◽  
Marcin Kowanetz ◽  
Hideki Niimi ◽  
Carl-Henrik Heldin ◽  
Aristidis Moustakas
Keyword(s):  
Target Genes ◽  
Transforming Growth Factor ◽  
Epithelial Mesenchymal Transition ◽  
Smooth Muscle Actin ◽  
Expression Patterns ◽  
Ectopic Expression ◽  
Dominant Negative ◽  
Type I ◽  
Mesenchymal Transition ◽  
Smad Signaling

Epithelial-mesenchymal transition (EMT) contributes to normal tissue patterning and carcinoma invasiveness. We show that transforming growth factor (TGF)-β/activin members, but not bone morphogenetic protein (BMP) members, can induce EMT in normal human and mouse epithelial cells. EMT correlates with the ability of these ligands to induce growth arrest. Ectopic expression of all type I receptors of the TGF-β superfamily establishes that TGF-β but not BMP pathways can elicit EMT. Ectopic Smad2 or Smad3 together with Smad4 enhanced, whereas dominant-negative forms of Smad2, Smad3, or Smad4, and wild-type inhibitory Smad7, blocked TGF-β–induced EMT. Transcriptomic analysis of EMT kinetics identified novel TGF-β target genes with ligand-specific responses. Using a TGF-β type I receptor that cannot activate Smads nor induce EMT, we found that Smad signaling is critical for regulation of all tested gene targets during EMT. One such gene, Id2, whose expression is repressed by TGF-β1 but induced by BMP-7 is critical for regulation of at least one important myoepithelial marker, α-smooth muscle actin, during EMT. Thus, based on ligand-specific responsiveness and evolutionary conservation of the gene expression patterns, we begin deciphering a genetic network downstream of TGF-β and predict functional links to the control of cell proliferation and EMT.

Intratubular epithelial-mesenchymal transition and tubular atrophy after kidney injury in mice

2020 ◽  
Vol 319 (4) ◽  
pp. F579-F591
Author(s):  
Noriyuki Yamashita ◽  
Tetsuro Kusaba ◽  
Tomohiro Nakata ◽  
Aya Tomita ◽  
Tomoharu Ida ◽  
...  
Keyword(s):  
Growth Factor ◽  
Acute Phase ◽  
Transforming Growth Factor ◽  
Epithelial Mesenchymal Transition ◽  
Chronic Phase ◽  
Transforming Growth Factor Β ◽  
Tubular Atrophy ◽  
Mesenchymal Transition

Tubular atrophy is a common pathological feature of kidney fibrosis. Although fibroblasts play a predominant role in tissue fibrosis, the role of repairing tubular epithelia in tubular atrophy is unclear. We demonstrated the essential role of focal adhesion kinase (FAK)-mediated intratubular epithelial-mesenchymal transition (EMT) in the pathogenesis of tubular atrophy after severe ischemia-reperfusion injury (IRI). Actively proliferating tubular epithelia undergoing intratubular EMT were noted in the acute phase of severe IRI, resulting in tubular atrophy in the chronic phase, reflecting failed tubular repair. Furthermore, FAK was phosphorylated in the tubular epithelia in the acute phase of severe IRI, and its inhibition ameliorated both tubular atrophy and interstitial fibrosis in the chronic phase after injury. In vivo clonal analysis of single-labeled proximal tubular epithelial cells after IRI using proximal tubule reporter mice revealed substantial clonal expansion after IRI, reflecting active epithelial proliferation during repair. The majority of these proliferating epithelia were located in atrophic and nonfunctional tubules, and FAK inhibition was sufficient to prevent tubular atrophy. In vitro, transforming growth factor-β induced FAK phosphorylation and an EMT phenotype, which was also prevented by FAK inhibition. In an in vitro tubular epithelia gel contraction assay, transforming growth factor-β treatment accelerated gel contraction, which was suppressed by FAK inhibition. In conclusion, injury-induced intratubular EMT is closely related to tubular atrophy in a FAK-dependent manner.

scholarly journals Roles of TGF β and FGF Signals in the Lens: Tropomyosin Regulation for Posterior Capsule Opacity

2018 ◽  
Vol 19 (10) ◽  
pp. 3093 ◽  
Author(s):  
Eri Kubo ◽  
Teppei Shibata ◽  
Dhirendra Singh ◽  
Hiroshi Sasaki
Keyword(s):  
Growth Factor ◽  
Transforming Growth Factor ◽  
Epithelial Mesenchymal Transition ◽  
Posterior Capsule ◽  
Peroxiredoxin 6 ◽  
Knock Out ◽  
Mesenchymal Transition ◽  
Lens Extraction ◽  
Elevated Expression ◽  
Tgf Β1

Transforming growth factor (TGF) β and fibroblast growth factor (FGF) 2 are related to the development of posterior capsule opacification (PCO) after lens extraction surgery and other processes of epithelial–mesenchymal transition (EMT). Oxidative stress seems to activate TGF β1 largely through reactive oxygen species (ROS) production, which in turn alters the transcription of several survival genes, including lens epithelium-cell derived growth factor (LEDGF). Higher ROS levels attenuate LEDGF function, leading to down-regulation of peroxiredoxin 6 (Prdx6). TGF β is regulated by ROS in Prdx6 knock-out lens epithelial cells (LECs) and induces the up-regulation of tropomyosins (Tpms) 1/2, and EMT of LECs. Mouse and rat PCO are accompanied by elevated expression of Tpm2. Further, the expression of Tpm1/2 is induced by TGF β2 in LECs. Importantly, we previously showed that TGF β2 and FGF2 play regulatory roles in LECs in a contrasting manner. An injury-induced EMT of a mouse lens as a PCO model was attenuated in the absence of Tpm2. In this review, we present findings regarding the roles of TGF β and FGF2 in the differential regulation of EMT in the lens. Tpms may be associated with TGF β2- and FGF2-related EMT and PCO development.

Sign in / Sign up

Export Citation Format

Share Document