Perturbed meibomian gland and tarsal plate morphogenesis by excess TGFα in eyelid stroma

Dong, Fei; Liu, Chia-Yang; Yuan, Yong; Zhang, Yujin; Li, Wei; Call, Mindy K.; Zhang, Liyun; Chen, Yongxiong; Liu, Zuguo; Kao, Winston W.‐Y.

doi:10.1016/j.ydbio.2015.09.003

Cited by 9 publications

(5 citation statements)

References 35 publications

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“…34 The double transgenic mouse KR/TGF-α was created to express TGF-α in corneal stromal cells with Dox administration. The eyes of Dox-induced KR/TGF-α mice looked normal and transparent 20 ; no dramatic phenotypes were observed. This inconsistent consequence of ectopic expression of TGF-α in cornea of these two mouse strains is probably owing to different expression levels of TGF-α in their corneal stroma, which suggested that lower TGF-α level was produced in KR/TGF-α mouse strain.…”

Section: Discussionmentioning

confidence: 94%

“…This observation was unique and distinct from phenotypic changes found in other transgenic mouse lines that overexpress TGF-α and fibroblast growth factor-7 in eyelid stroma and corneal epithelial cells, respectively. 20,21 It has been reported that overexpression of EGF and/or EGFR caused apoptosis of cultured epithelial cells in vitro. 22,23 Thus, it is likely that excess TGF-α promoted corneal epithelial cell proliferation during embryonic development.…”

Section: Discussionmentioning

confidence: 99%

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Excess Transforming Growth Factor-α Changed the Cell Properties of Corneal Epithelium and Stroma

Zhang

Yuan

Yeh

et al. 2020

Invest. Ophthalmol. Vis. Sci.

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This study is to investigate the corneal anomaly caused by excess transforming growth factor-α (TGF-α) during mouse development. METHODS. Bitransgenic Kera RT /TGF-α mice, generated via cross-mating tetO-TGF-α and Kera RT mice, were induced to overexpress TGF-α by doxycycline commencing at embryonic day 0 or postnatal day 0 to different developmental stages. Bitransgenic mice with doxycycline induction were defined as TGF-α ECK mice (TGF-α excess expression by corneal keratocytes). Mouse eyes were examined by hematoxylin and eosin staining, immunofluorescent staining and transmission electron microscopy. Protein and RNA from mouse cornea were subjected to western blotting and real-time quantitative polymerase chain reaction. RESULTS. In TGF-α ECK mice, TGF-α overexpression resulted in corneal opacity. Excess TGFα initially caused corneal epithelial hyperplasia and subsequent epithelium degeneration as the mouse developed, which was accompanied by gradually diminished K12 expression from the periphery of corneal epithelium and increased K13 expression toward the corneal center. Interestingly, K14 was detected in all layers of corneal epithelium of TGF-α ECK mice, whereas it was limited at basal layer of controls. Transmission electron microscopy showed desmosome loss between corneal epithelial cells of TGF-α ECK mice. In TGF-α ECK mice, keratocan expression was abolished; α-SMA expression was increased while expression of Col1a1, Col1a2, and Col5a1 was diminished. Cell proliferation increased in the corneal epithelium and stroma, but not in the endothelium of TGF-α ECK mice. CONCLUSIONS. Excess TGF-α had detrimental effects on corneal morphogenesis during mouse development in that it changed the cell fate of corneal epithelial cells to assume conjunctival phenotypic expression of K13, and keratocytes to myofibroblast phenotype.

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Section: Discussionmentioning

confidence: 94%

Section: Discussionmentioning

confidence: 99%

Excess Transforming Growth Factor-α Changed the Cell Properties of Corneal Epithelium and Stroma

Zhang

Yuan

Yeh

et al. 2020

Invest. Ophthalmol. Vis. Sci.

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“…Meibomian gland morphogenesis commences at E18.5. The first sign of gland development is detected at the lid junction where the mesenchyme of neural crest and mesoderm origin underneath the future gland primordium starts to condense (Dong et al, 2015). The overlaying epithelial cells of ectoderm origin form the epithelium placode.…”

Section: Eyelid and Meibomian Gland Morphogenesis In Mousementioning

confidence: 99%

“…As a mitogen, TGFα can stimulate the proliferation of eyelid mesenchymal cells. In KR/TGFα transgenic mice, excess TGFα secreted by keratocytes stimulates hyper proliferation of eyelid tenocytes in eyelid tendon and tarsal plate (Dong et al, 2015). Reneker, et al, using αA-crystallin-TGFα transgenic mouse showed that as early as E15, TGFα could act as a chemoattractant to induce periocular mesenchymal cell migration towards the lens from both an anterior and posterior direction (Reneker, Silversides, Patel, & Overbeek, 1995).…”

Section: Egfr Signaling In Eyelid Morphogenesismentioning

confidence: 99%

“…Tarsal plate offers a scaffold for meibomian gland morphogenesis. Hyper proliferative tarsal plate cells triggered by TGFα accumulate around the meibomian glands, therefore perturbing meibomian gland morphogenesis due to improper tarsal plate formation and altered mesenchymal–epithelial interactions (Dong et al, 2015). …”

Section: Egfr Signaling In Meibomian Gland Morphogenesismentioning

confidence: 99%

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Role of EGF receptor signaling on morphogenesis of eyelid and meibomian glands

Dong

Call

Xia

et al. 2017

Experimental Eye Research

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The epidermal growth factor receptor (EGFR) signaling has a pivotal role in the regulation of morphogenesis during development and maintenance of homeostasis in adult eyelid and its adnexa. Studies have demonstrated that during eyelid morphogenesis the EGFR signaling pathway is responsible for keratinocyte and mesenchymal cell proliferation and migration at the eyelid tip. For meibomian gland morphogenesis, EGFR signaling activation stimulates meibomian gland epithelial cell proliferation. EGFR signaling pathway functions through multiple downstream signals such as ERK, Rho/ROCK and integrin and is regulated by a variety of upstream signals including Adam17, GPR48 and FGFR signaling. Herein we review the literature that describe the role of EGFR and its related signaling pathways in eyelid and meibomian gland morphogenesis.

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Genetically modified laboratory mice with sebaceous glands abnormalities

Ehrmann¹,

Schneider²

2016

Cell. Mol. Life Sci.

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Sebaceous glands (SG) are exocrine glands that release their product by holocrine secretion, meaning that the whole cell becomes a secretion following disruption of the membrane. SG may be found in association with a hair follicle, forming the pilosebaceous unit, or as modified SG at different body sites such as the eyelids (Meibomian glands) or the preputial glands. Depending on their location, SG fulfill a number of functions, including protection of the skin and fur, thermoregulation, formation of the tear lipid film, and pheromone-based communication. Accordingly, SG abnormalities are associated with several diseases such as acne, cicatricial alopecia, and dry eye disease. An increasing number of genetically modified laboratory mouse lines develop SG abnormalities, and their study may provide important clues regarding the molecular pathways regulating SG development, physiology, and pathology. Here, we summarize in tabulated form the available mouse lines with SG abnormalities and, focusing on selected examples, discuss the insights they provide into SG biology and pathology. We hope this survey will become a helpful information source for researchers with a primary interest in SG but also as for researchers from unrelated fields that are unexpectedly confronted with a SG phenotype in newly generated mouse lines.

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Perturbed meibomian gland and tarsal plate morphogenesis by excess TGFα in eyelid stroma

Cited by 9 publications

References 35 publications

Excess Transforming Growth Factor-α Changed the Cell Properties of Corneal Epithelium and Stroma

Excess Transforming Growth Factor-α Changed the Cell Properties of Corneal Epithelium and Stroma

Role of EGF receptor signaling on morphogenesis of eyelid and meibomian glands

Genetically modified laboratory mice with sebaceous glands abnormalities

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