Apoptosis of oral epithelial cells in oral lichen planus caused by upregulation of BMP‐4

Kim, S.-G.; Chae, Chang-Hoon; Cho, B.-O.; Kim, H.-N.; Kim, H.-J.; Kim, Il Sup; Choi, Je‐Yong

doi:10.1111/j.1600-0714.2005.00373.x

Cited by 49 publications

(37 citation statements)

References 27 publications

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“…Based on the results of the microarrays and quantitative RT-PCR, it seems clear that expression of MMP-3 in HDFs is more affected than that of MMP-1. BMP-4 was reported to induce the expression of MMP-1 and MMP-3 in oral epithelium (25). However, our results did not confirm this ( Table 1).…”

Section: Discussioncontrasting

confidence: 57%

Downregulation of matrix metalloproteinases in hyperplastic dental follicles results in abnormal tooth eruption

Kim

Kim²,

Chae³

et al. 2008

BMB Reports

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In this study, we compared the gene expression profiles of non-syndromic hyperplastic dental follicle (HDF) fibroblasts and normal dental follicle (NDF) fibroblasts using cDNA microarrays, quantitative PCR, and immunohistochemical staining. Microarray analysis showed that several collagens genes were upregulated in the HDF's, including collagen types I, IV, VIII, and XI and TIMP-1, -3, and -4 (fold ratio ＞ 2.0). In contrast, the expression of MMP-1, -3, -10, and -16 together with IL-8 was more than two fold downregulated.

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Section: Discussioncontrasting

confidence: 57%

Downregulation of matrix metalloproteinases in hyperplastic dental follicles results in abnormal tooth eruption

Kim

Kim²,

Chae³

et al. 2008

BMB Reports

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“…Interestingly, other studies have shown that the inhibition of BMP signaling by overexpression of Nog under a Krt5 promoter in the epidermis also results in alterations in eyelid epithelial differentiation, and the levels of involucrin and loricrin are reduced (Sharov et al, 2003). Conversely, the addition of Bmp4 to cultured human oral epithelium increases the expression of involucrin (Kim et al, 2006). These studies suggest that BMP signaling regulates the differentiation of suprabasal cells in stratified epithelium.…”

Section: Ectopic Activation Of Bmp Signaling In the Epitheliummentioning

confidence: 71%

BMP signaling in the development of the mouse esophagus and forestomach

et al. 2010

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SUMMARYThe stratification and differentiation of the epidermis are known to involve the precise control of multiple signaling pathways. By contrast, little is known about the development of the mouse esophagus and forestomach, which are composed of a stratified squamous epithelium. Based on prior work in the skin, we hypothesized that bone morphogenetic protein (BMP) signaling is a central player. To test this hypothesis, we first used a BMP reporter mouse line harboring a BRE-lacZ allele, along with in situ hybridization to localize transcripts for BMP signaling components, including various antagonists. We then exploited a Shh-Cre allele that drives recombination in the embryonic foregut epithelium to generate gain-or loss-of-function models for the Bmpr1a (Alk3) receptor. In gain-of-function (Shh-Cre;Rosa26 CAG-loxpstoploxp-caBmprIa) embryos, high levels of ectopic BMP signaling stall the transition from simple columnar to multilayered undifferentiated epithelium in the esophagus and forestomach. In loss-of-function experiments, conditional deletion of the BMP receptor in Shh-Cre;Bmpr1a flox/flox embryos allows the formation of a multilayered squamous epithelium but this fails to differentiate, as shown by the absence of expression of the suprabasal markers loricrin and involucrin. Together, these findings suggest multiple roles for BMP signaling in the developing esophagus and forestomach.

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“…Additionally, BMP4 is known to induce apoptosis in a p53 (TRP53)-dependent manner in cancer cells as well as oral epithelial cells (Fukuda et al, 2006;Kim et al, 2006;Haubold et al, 2010). p53 tumor suppressor is a transcription factor that induces cell growth arrest and apoptosis (Kerr et al, 1972).…”

Section: Introductionmentioning

confidence: 99%

Augmented BMP signaling in the neural crest inhibits nasal cartilage morphogenesis by inducing p53-mediated apoptosis

et al. 2015

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Bone morphogenetic protein (BMP) signaling plays many roles in skull morphogenesis. We have previously reported that enhanced BMP signaling through the BMP type IA receptor (BMPR1A) in cranial neural crest cells causes craniosynostosis during postnatal development. Additionally, we observed that 55% of Bmpr1a mutant mice show neonatal lethality characterized by a distended gastrointestinal tract. Here, we show that severely affected mutants exhibit defective nasal cartilage, failure of fusion between the nasal septum and the secondary palate, and higher levels of phosphorylated SMAD1 and SMAD5 in the nasal tissue. TUNEL demonstrated an increase in apoptosis in both condensing mesenchymal tissues and cartilage of the nasal region in mutants. The levels of p53 (TRP53) tumor suppressor protein were also increased in the same tissue. Injection of pifithrin-α, a chemical inhibitor of p53, into pregnant mice prevented neonatal lethality while concomitantly reducing apoptosis in nasal cartilage primordia, suggesting that enhanced BMP signaling induces p53-mediated apoptosis in the nasal cartilage. The expression of Bax and caspase 3, downstream targets of p53, was increased in the mutants; however, the p53 expression level was unchanged. It has been reported that MDM2 interacts with p53 to promote degradation. We found that the amount of MDM2-p53 complex was decreased in all mutants, and the most severely affected mutants had the largest decrease. Our previous finding that the BMP signaling component SMAD1 prevents MDM2-mediated p53 degradation coupled with our new data indicate that augmented BMP signaling induces p53-mediated apoptosis by prevention of p53 degradation in developing nasal cartilage. Thus, an appropriate level of BMP signaling is required for proper craniofacial morphogenesis.

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Apoptosis of oral epithelial cells in oral lichen planus caused by upregulation of BMP‐4

Cited by 49 publications

References 27 publications

Downregulation of matrix metalloproteinases in hyperplastic dental follicles results in abnormal tooth eruption

Downregulation of matrix metalloproteinases in hyperplastic dental follicles results in abnormal tooth eruption

BMP signaling in the development of the mouse esophagus and forestomach

Augmented BMP signaling in the neural crest inhibits nasal cartilage morphogenesis by inducing p53-mediated apoptosis

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