Perlecan-Deficient Mutation Impairs Corneal Epithelial Structure

Inomata, Takenori; Ebihara, Nobuyuki; Funaki, Toshinari; Matsuda, Akira; Watanabe, Yasuo; Liang, Ning; Xu, Zhuo; Murakami, Akira; Arikawa‐Hirasawa, Eri

doi:10.1167/iovs.11-8742

Cited by 31 publications

(28 citation statements)

References 40 publications

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“…The first transgenic model was generated by genomic deletion of exon 3 (designated as Hspg2 Δ3/Δ3), which encodes two out of the three SGD consensus sites for HS attachment in domain I [116]. These mice are fertile, despite having reduced amounts of HS, and show lens degeneration three weeks post birth [116], indicating a key role for the HS chains in lens capsule homeostasis [117]. Further, the HS-deficient mice have narrowing of an experimentally occluded carotid artery due to augmented intimal hyperplasia concomitant with smooth muscle cell proliferation [118], as well as impaired tumor angiogenesis, tumorigenesis, and delayed wound healing [119].…”

Section: Defective Perlecan Is Coupled With Genetic Conditions Penetrmentioning

confidence: 99%

A current view of perlecan in physiology and pathology: A mosaic of functions

2017

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Perlecan, a large basement membrane heparan sulfate proteoglycan, is expressed in a wide array of tissues where it regulates diverse cellular processes including bone formation, inflammation, cardiac development, and angiogenesis. Here we provide a contemporary review germane to the biology of perlecan encompassing its genetic regulation as well as an analysis of its modular protein structure as it pertains to function. As perlecan signaling from the extracellular matrix converges on master regulators of autophagy, including AMPK and mTOR, via a specific interaction with vascular endothelial growth factor receptor 2, we specifically focus on the mechanism of action of perlecan in autophagy and angiogenesis and contrast the role of endorepellin, the C-terminal fragment of perlecan, in these cellular and morphogenic events.

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Section: Defective Perlecan Is Coupled With Genetic Conditions Penetrmentioning

confidence: 99%

A current view of perlecan in physiology and pathology: A mosaic of functions

2017

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“…Perlecan has been shown to participate in many biological processes in different tissues, including regulation of wound healing, cell proliferation, and cell survival (Rossi et al, 2003; Sher et al, 2006; Zhou et al, 2004). Inomata et al (2012) found a thin and poorly-differentiated corneal epithelium in perlecan-deficient mice and suggested that BM perlecan was critical for normal epithelium formation and terminal differentiation. The current study found that both corneal epithelial cells and keratocytes produce perlecan protein.…”

mentioning

confidence: 94%

Epithelial basement membrane proteins perlecan and nidogen-2 are up-regulated in stromal cells after epithelial injury in human corneas

Torricelli

Marino

Santhanam

et al. 2015

Experimental Eye Research

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The epithelial basement membrane (BM) is a specialized extracellular matrix that has been shown to have a critical role in corneal development, wound healing, and disease. Although the epithelial BM contributes to corneal homeostasis, relatively little is know about non-epithelial production of its components that may be important in defective regeneration of the epithelial basement membrane associated with opacity after photorefractive keratectomy. The purpose of the current study was to investigate stromal production of corneal epithelial BM proteins in wounded human corneas using immunohistochemistry. A total of five unwounded control eyes and five 30-minute epithelial-wounded corneas were obtained from fresh corneoscleral buttons removed from human eyes enucleated due to choroidal melanoma with normal anterior segments. In the wounded corneas, an eight mm patch of central corneal epithelium and epithelial BM was removed with a Beaver blade when the patient was under general anesthesia. Immunohistochemical analyses were performed to detect perlecan and nidogen-2 proteins–important components of the epithelial BM lamina lucida and lamina densa zones. Perlecan and nidogen-2 proteins were detected in the BM itself and at low levels in keratocytes in all unwounded corneas. After epithelial injury, both perlecan and nidogen-2 was expressed at high levels in stromal keratocytes, including superficial keratocytes in the early phases of apoptosis. Thus, after epithelial and epithelial BM injury, stromal keratocytes contribute important perlecan and nidogen-2 components to the regenerating epithelial BM.

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“…Perlecan is one of the few genes in the human genome that is expressed by both vascular (6 -9) and avascular tissues, such as cartilage (10), and is localized at the apical cell surface (11,12) as well as in the basement membranes of both epithelial and endothelial lined tissues (6,13,14). Based on its widespread expression in both embryonic (10) and adult (13) life and its ability to engage various receptor tyrosine kinases (15), perlecan regulates various biological processes, including cell adhesion (16), lipid metabolism (17), thrombosis (18), apoptosis (19), biomechanical properties of blood vessels and cartilage (20,21), premature rupture of fetal membranes (22), epidermal formation (23), endochondral bone (24) and enamel organ (25) formation, osteophyte formation (26), and corneal structure (27). Moreover, perlecan binds various growth factors (28 -32), and its expression is often deregulated in several types of cancer (33)(34)(35).…”

mentioning

confidence: 99%

Endorepellin Evokes Autophagy in Endothelial Cells

Poluzzi¹,

Casulli²,

Goyal

et al. 2014

Journal of Biological Chemistry

120

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Background: Endorepellin inhibits angiogenesis by simultaneously binding the ␣2␤1 integrin and VEGFR2, attenuating the PI3K/Akt/mTOR and PKC/JNK/AP1 signaling pathways. Results: Endorepellin evokes autophagy by inducing Beclin 1 and LC3 downstream of VEGFR2 in a Peg3-dependent manner. Conclusion: Endorepellin causes endothelial cell autophagy through VEGFR2 independent of the ␣2␤1 integrin. Significance: Endorepellin-evoked endothelial cell autophagy represents a promising strategy for angiostatic-based therapeutics.

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Perlecan-Deficient Mutation Impairs Corneal Epithelial Structure

Cited by 31 publications

References 40 publications

A current view of perlecan in physiology and pathology: A mosaic of functions

A current view of perlecan in physiology and pathology: A mosaic of functions

Epithelial basement membrane proteins perlecan and nidogen-2 are up-regulated in stromal cells after epithelial injury in human corneas

Endorepellin Evokes Autophagy in Endothelial Cells

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