p63 in corneal and epidermal differentiation

Novelli, Flavia; Ganini, Carlo; Melino, Gerry; Nucci, Carlo Alberto; Han, Yuyi; Shi, Yufang; Wang, Ying; Candi, Eleonora

doi:10.1016/j.bbrc.2022.04.022

Cited by 13 publications

(12 citation statements)

References 96 publications

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“…In the case of HAC, it is likely that these factors can contribute to the normal physiology and homeostasis of the grafted cornea, and in vivo samples are able to express p63, once implanted in vivo. As the role of p63 has been previously described as essential in controlling epithelial proliferation, differentiation and development (Novelli et al, 2022), these results are in agreement with previous reports suggesting that mesenchymal stem cells could have the potential to improve tissue regeneration, and may have in vivo differentiation potential (Garzón et al, 2020).…”

Section: Discussionsupporting

confidence: 93%

“…After in vivo implantation, these corneas were able to integrate in the host animal after the established follow-up time. Interestingly, the epithelial-like cell layer found in the HAC model kept ex vivo was not able to express p63, a regulator of epithelial differentiation and morphogenesis ( Chee et al, 2006 ; Novelli et al, 2022 ), confirming the non-epithelial phenotype of these cells. However, the use of corneal epithelial cells in OAC models was indeed associated with the positive expression of this marker, as it is the case of the human native cornea.…”

Section: Discussionmentioning

confidence: 84%

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Development of stromal differentiation patterns in heterotypical models of artificial corneas generated by tissue engineering

Blanco-Elices

Morales-Álvarez

Chato‐Astrain

et al. 2023

Front. Bioeng. Biotechnol.

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Purpose: We carried out a histological characterization analysis of the stromal layer of human heterotypic cornea substitutes generated with extra-corneal cells to determine their putative usefulness in tissue engineering.Methods: Human bioartificial corneas were generated using nanostructured fibrin-agarose biomaterials with corneal stromal cells immersed within. To generate heterotypical corneas, umbilical cord Wharton’s jelly stem cells (HWJSC) were cultured on the surface of the stromal substitutes to obtain an epithelial-like layer. These bioartificial corneas were compared with control native human corneas and with orthotypical corneas generated with human corneal epithelial cells on top of the stromal substitute. Both the corneal stroma and the basement membrane were analyzed using histological, histochemical and immunohistochemical methods in samples kept in culture and grafted in vivo for 12 months in the rabbit cornea.Results: Our results showed that the stroma of the bioartificial corneas kept ex vivo showed very low levels of fibrillar and non-fibrillar components of the tissue extracellular matrix. However, in vivo implantation resulted in a significant increase of the contents of collagen, proteoglycans, decorin, keratocan and lumican in the corneal stroma, showing higher levels of maturation and spatial organization of these components. Heterotypical corneas grafted in vivo for 12 months showed significantly higher contents of collagen fibers, proteoglycans and keratocan. When the basement membrane was analyzed, we found that all corneas grafted in vivo showed intense PAS signal and higher contents of nidogen-1, although the levels found in human native corneas was not reached, and a rudimentary basement membrane was observed using transmission electron microscopy. At the epithelial level, HWJSC used to generate an epithelial-like layer in ex vivo corneas were mostly negative for p63, whereas orthotypical corneas and heterotypical corneas grafted in vivo were positive.Conclusion: These results support the possibility of generating bioengineered artificial corneas using non-corneal HWJSC. Although heterotypical corneas were not completely biomimetic to the native human corneas, especially ex vivo, in vivo grafted corneas demonstrated to be highly biocompatible, and the animal cornea became properly differentiated at the stroma and basement membrane compartments. These findings open the door to the future clinical use of these bioartificial corneas.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 84%

Development of stromal differentiation patterns in heterotypical models of artificial corneas generated by tissue engineering

Blanco-Elices

Morales-Álvarez

Chato‐Astrain

et al. 2023

Front. Bioeng. Biotechnol.

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“…Moreover, the epidermal fate acquisition is associated with the BMP signaling pathway via the Wnt signaling pathway, but the detailed molecular mechanism remains to be clarified (Zhu et al, 2014). P63 is the first identified transcription factor specifically expressed in cells accepting epidermal fate, and TAp63α is the first P63 subunit reported to express in epidermal morphogenesis (Novelli et al, 2022). Previous studies found that TAp63α heterotopic expression activates keratin K14 in cell lines and lungs of transgenic mice, indicating the induction of keratin K14 by TAp63α during epidermal morphogenesis (Koster & Roop, 2007).…”

Section: Cell Differentiation In Epidermal Stratificationmentioning

confidence: 99%

Regulation of epidermal stratification and development by basal keratinocytes

Yin

2023

Journal Cellular Physiology

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The epidermis is a stratified squamous epithelium distributed in the outermost layer of the skin and is intimately involved in the formation of a physical barrier to pathogens. Basal keratinocytes possess the properties of stem cells and play an essential role in epidermal development and skin damage recovery. Therefore, understanding the molecular mechanism of how basal keratinocytes participate in epidermal development and stratification is vital for preventing and treating skin lesions. During epidermal morphogenesis, the symmetric division of basal keratinocytes contributes to the extension of skin tissues, while their asymmetric division and migration facilitate epidermal stratification. In this review, we summarize the process of epidermal stratification and illustrate the molecular mechanisms underlying epidermal morphogenesis. Furthermore, we discuss the coordination of multiple signaling pathways and transcription factors in epidermal stratification, together with the roles of cell polarity and cell dynamics during the process.

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“…In contrast to the comparatively infrequent mutations of the p63 gene, p53 is often downregulated or mutated in tumors ( 49 ). To be specific, more than 95% of p53 mutations lie in the DBD, a mutated hotspot located in the DBD (such as R175H), resulting in structural instability and polarity disorder ( 50 ).…”

Section: P53 Prion-like Behavior Affects P63mentioning

confidence: 99%

The dual role of p63 in cancer

Yang

Xiong

et al. 2023

Front. Oncol.

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The p53 family is made up of three transcription factors: p53, p63, and p73. These proteins are well-known regulators of cell function and play a crucial role in controlling various processes related to cancer progression, including cell division, proliferation, genomic stability, cell cycle arrest, senescence, and apoptosis. In response to extra- or intracellular stress or oncogenic stimulation, all members of the p53 family are mutated in structure or altered in expression levels to affect the signaling network, coordinating many other pivotal cellular processes. P63 exists as two main isoforms (TAp63 and ΔNp63) that have been contrastingly discovered; the TA and ΔN isoforms exhibit distinguished properties by promoting or inhibiting cancer progression. As such, p63 isoforms comprise a fully mysterious and challenging regulatory pathway. Recent studies have revealed the intricate role of p63 in regulating the DNA damage response (DDR) and its impact on diverse cellular processes. In this review, we will highlight the significance of how p63 isoforms respond to DNA damage and cancer stem cells, as well as the dual role of TAp63 and ΔNp63 in cancer.

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p63 in corneal and epidermal differentiation

Cited by 13 publications

References 96 publications

Development of stromal differentiation patterns in heterotypical models of artificial corneas generated by tissue engineering

Development of stromal differentiation patterns in heterotypical models of artificial corneas generated by tissue engineering

Regulation of epidermal stratification and development by basal keratinocytes

The dual role of p63 in cancer

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