Integrins in lens development and disease

Walker, James B.; Menko, A. Sue

doi:10.1016/j.exer.2008.06.020

Cited by 68 publications

(66 citation statements)

References 93 publications

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“…Integrins are a large family of 24 heterodimers formed from eight β subunits and α subunits that have been identified. Integrins play a role in communicating messages between the cell and the environment via extracellular matrix interactions [69][70][71] . The binding to extracellular matrix to integrins results cytoplasmic signals in the integrin-expressing cell contributing to cell growth, differentiation, invasion, metastasis, and survival [65,[72][73][74] .…”

Section: Integrins and Biliary Fibrosismentioning

confidence: 99%

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Involvement of cholangiocyte proliferation in biliary fibrosis

Priester

Wise²,

Glaser

2010

WJGP

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Cholangiocytes are the epithelial cells that line the biliary tree. In the adult liver, they are a mitotically dormant cell population, unless ductular reaction is triggered by injury. The ability of cholangiocytes to proliferate is important in many different human pathological liver conditions that target this cell type, which are termed cholangiopathies (i.e. primary biliary cirrhosis, primary sclerosing cholangitis and biliary atresia). In our article, we provide background information on the morphological and functional heterogeneity of cholangiocytes, summarize what is currently known about their proliferative processes, and briefly describe the diseases that target these cells. In addition, we address recent findings that suggest cholangiocyte involvement in epithelialtomesenchymal transformation and liver fibrosis, and propose directions for future studies.

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Section: Integrins and Biliary Fibrosismentioning

confidence: 99%

“…Integrins are a family of heterodimeric transmembrane glycoproteins composed of α and β chain protein subunits that act as cell surface receptors [69][70][71] . Integrins are a large family of 24 heterodimers formed from eight β subunits and α subunits that have been identified.…”

Section: Integrins and Biliary Fibrosismentioning

confidence: 99%

Involvement of cholangiocyte proliferation in biliary fibrosis

Priester

Wise²,

Glaser

2010

WJGP

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“…Smad3 phosphorylation was not detected in αν integrin null lenses (Mamuya et al, 2014). Integrins activate TGFβ and induce lens PCO and ASC (Walker and Menko, 2009) (Fig. 5).…”

Section: Gene Introduction To An Injured Mouse Lensmentioning

confidence: 99%

The murine lens: A model to investigate in vivo epithelial–mesenchymal transition

Shirai

Tanaka

Lovicu

et al. 2017

Developmental Dynamics

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Epithelial–mesenchymal transition (EMT) produces myofibroblasts that contribute to the formation of fibrotic tissue with an impairment of tissue homeostasis and functionality. The crystalline lens of the eye is a unique transparent and isolated tissue. The lens vesicle becomes isolated from the surface ectoderm, its cells are all contained as they line the inner surface of the lens capsule. Clinically the formation of fibrotic tissue by the lens epithelial cells causes a type of cataract or opacification and contraction of the lens capsule postcataract surgery. Production of EMT in the intact animal lens by using specific gene transfer to the lens or experimental lens injury has been shown to be a powerful tool to investigate EMT processes. It is not easy to uncover whether the origin of the myofibroblast is epithelial cell‐derived or from other cell lineages in fibrotic tissues. However, myofibroblasts that appear in the crystalline lens pathology are totally derived from the lens epithelial cells for the reasons mentioned above. Here, we report on different animal models of lens EMT, using either transgenic approaches or injury to study the biological aspects of EMT. Developmental Dynamics 247:340–345, 2018. © 2017 The Authors Developmental Dynamics published by Wiley Periodicals, Inc. on behalf of American Association of Anatomists

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“…Pathological lens EMT is associated with increased expression of mesenchymal α-smooth muscle actin, increased deposition of the ECM proteins collagen IV and fibronectin, and decreased expression of epithelial E-cadherin (Walker and Menko, 2009). However, we observed no change in Ecadherin, collagen IV or α-smooth muscle actin expression in Crim1 mutants, effectively excluding the hypothesis that Crim1 regulates EMT during lens development (Fig.…”

Section: Crim1 Colocalizes With β1 Integrin In Le Cell Membranesmentioning

confidence: 99%

“…β1 integrin forms the largest integrin subfamily as it can assemble into heterodimers with 12 different α subunits. Studies of lens development have shown that β1 integrin is expressed in LE cells and LF cells (Bassnett et al, 1999;Menko and Philip, 1995;Wederell et al, 2005), whereas β3 and β4 integrins are also expressed in developing lens, together with αv and α6, respectively [reviewed by Walker and Menko (2009)]. Although knockout of the mouse β1 integrin gene (Itgb1) leads to peri-implantation lethality (Fassler and Meyer, 1995;Stephens et al, 1995), conditional knockout of Itgb1 in lens results in cataract and microphthalmia due to apoptosis of LE cells and loss of the LE cell phenotype (Samuelsson et al, 2007;Simirskii et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

Crim1 regulates integrin signaling in murine lens development

Zhang¹,

Fan²,

Ho³

et al. 2016

Journal of Cell Science

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The developing lens is a powerful system for investigating the molecular basis of inductive tissue interactions and for studying cataract, the leading cause of blindness. The formation of tightly controlled cell-cell adhesions and cell-matrix junctions between lens epithelial (LE) cells, between lens fiber (LF) cells, and between these two cell populations enables the vertebrate lens to adopt a highly ordered structure and acquire optical transparency. Adhesion molecules are thought to maintain this ordered structure, but little is known about their identity or interactions. Cysteine-rich motor neuron 1 (Crim1), a type I transmembrane protein, is strongly expressed in the developing lens and its mutation causes ocular disease in both mice and humans. How Crim1 regulates lens morphogenesis is not understood. We identified a novel ENU-induced hypomorphic allele of Crim1, Crim1 glcr11 , which in the homozygous state causes cataract and microphthalmia. Using this and two other mutant alleles, Crim1 null and Crim1 cko , we show that the lens defects in Crim1 mouse mutants originate from defective LE cell polarity, proliferation and cell adhesion. Crim1 adhesive function is likely to be required for interactions both between LE cells and between LE and LF cells. We show that Crim1 acts in LE cells, where it colocalizes with and regulates the levels of active β1 integrin and of phosphorylated FAK and ERK. The RGD and transmembrane motifs of Crim1 are required for regulating FAK phosphorylation. These results identify an important function for Crim1 in the regulation of integrin-and FAKmediated LE cell adhesion during lens development.

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Integrins in lens development and disease

Cited by 68 publications

References 93 publications

Involvement of cholangiocyte proliferation in biliary fibrosis

Involvement of cholangiocyte proliferation in biliary fibrosis

The murine lens: A model to investigate in vivo epithelial–mesenchymal transition

Crim1 regulates integrin signaling in murine lens development

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