Genetic pathways in disorders of epidermal differentiation

Lopez-Pajares, Vanessa; Yan, Karen; Zarnegar, Brian; Jameson, Katherine L.; Khavari, Paul A.

doi:10.1016/j.tig.2012.10.005

Cited by 102 publications

(79 citation statements)

References 87 publications

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“…Signaling pathways involved in epidermal differentiation regulate keratin and desmosom- (Dong and Chen 2009;Leitner et al 2011;Lopez-Pajares et al 2013). However, links between these signaling pathways and the specific downstream transcription factors that regulate desmosomal protein expression have only been elucidated in a few instances.…”

Section: Transcriptional Regulation Of Desmosomal Componentsmentioning

confidence: 99%

Desmosomes: Regulators of Cellular Signaling and Adhesion in Epidermal Health and Disease

Johnson

Najor

Green

2014

Cold Spring Harbor Perspectives in Medicine

118

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Section: Transcriptional Regulation Of Desmosomal Componentsmentioning

confidence: 99%

Desmosomes: Regulators of Cellular Signaling and Adhesion in Epidermal Health and Disease

Johnson

Najor

Green

2014

Cold Spring Harbor Perspectives in Medicine

118

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“…Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and mitogenactivated protein kinase (MAPK), two key signaling pathways involved in inflammation [6,7], cell proliferation [8,9] and differentiation [8][9][10][11][12][13][14] in many cell types and tissues, have also been implicated in cutaneous wound healing [3,4]. However, the molecular mechanisms underlying cutaneous wound healing remain unclear.…”

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confidence: 99%

Epidermal CFTR Suppresses MAPK/NF-κB to Promote Cutaneous Wound Healing

Chen

et al. 2016

Cell Physiol Biochem

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Background: CFTR is implicated in cutaneous wound healing although the underlying mechanisms are not fully understood. In other cell types, CFTR is reported to regulate MAPK/ NF-κB signaling. We undertook the present study to explore a possible role of CFTR in regulating MAPK/NF-κB during cutaneous wound healing. Methods& Results: The splint-excisional and incisional wound healing models were used in CFTR mutant (DF508) mice. The cell-scratch model was used in a human keratinocyte line, HaCaT, in conjunction with CFTR knockdown or overexpression. The epidermal inflammation, keratinocyte proliferation and differentiation, as well as MAPK/NF-κB signaling were examined. Inhibitors of MAPK/NF-κB were also used. Results: Both DF508 mice and HaCaT cells with CFTR knockdown exhibited delayed cutaneous wound healing with exuberant inflammation, increased proliferation and aberrant differentiation. Knockdown of CFTR in HaCaT cells resulted in phosphorylation of ERK, p38 and IκBα. The disturbance of inflammation, proliferation and differentiation in HaCaT cells were reversed by CFTR overexpression or inhibition of MAPK or NF-κB. Conclusion: CFTR plays a role in suppressing MAPK/NF-κB to relieve inflammation, reduce proliferation and promote differentiation of keratinocytes, and thus promotes cutaneous wound healing.

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“…Epidermal homeostasis depends on balanced loss and repletion of keratinocyte strata. Disruption of homeostasis characterizes skin diseases affecting >20% of the population (Lopez-Pajares et al 2013), underscoring the importance of epidermal homeostasis to human health.…”

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confidence: 99%

CALML5 is a ZNF750- and TINCR-induced protein that binds stratifin to regulate epidermal differentiation

et al. 2015

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Outward migration of epidermal progenitors occurs with induction of hundreds of differentiation genes, but the identities of all regulators required for this process are unknown. We used laser capture microdissection followed by RNA sequencing to identify calmodulin-like 5 (CALML5) as the most enriched gene in differentiating outer epidermis. CALML5 mRNA was up-regulated by the ZNF750 transcription factor and then stabilized by the long noncoding RNA TINCR. CALML5 knockout impaired differentiation, abolished keratohyalin granules, and disrupted epidermal barrier function. Mass spectrometry identified SFN (stratifin/14-3-3σ) as a CALML5-binding protein.CALML5 interacts with SFN in suprabasal epidermis, cocontrols 13% of late differentiation genes, and modulates interaction of SFN to some of its binding partners. A ZNF750-TINCR-CALML5-SFN network is thus essential for epidermal differentiation.

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Genetic pathways in disorders of epidermal differentiation

Cited by 102 publications

References 87 publications

Desmosomes: Regulators of Cellular Signaling and Adhesion in Epidermal Health and Disease

Desmosomes: Regulators of Cellular Signaling and Adhesion in Epidermal Health and Disease

Epidermal CFTR Suppresses MAPK/NF-κB to Promote Cutaneous Wound Healing

CALML5 is a ZNF750- and TINCR-induced protein that binds stratifin to regulate epidermal differentiation

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