Disorder of the mevalonate pathway inhibits calcium-induced differentiation of keratinocytes

  • Authors:
    • Rui Jin
    • Xin Luo
    • Kang Luan
    • Li Liu
    • Liang‑Dan Sun
    • Sen Yang
    • Sheng‑Quan Zhang
    • Xue‑Jun Zhang
  • View Affiliations

  • Published online on: August 1, 2017     https://doi.org/10.3892/mmr.2017.7128
  • Pages: 4811-4816
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Abstract

Mutation of genes encoding the enzymes of the mevalonate pathway cause a variety of diseases, including skin disorders. Mutation of four genes in this pathway, including mevalonate kinase, phosphomevalonate kinase, mevalonate diphosphate decarboxylase and farnesyl diphosphate synthase, have demonstrated to be responsible for porokeratosis (PK). However, the pathogenesis of PK remains unclear. In the present study, specific enzyme inhibitors of the mevalonate pathway, including pravastatin (PRA), alendronate (ALD), farnesyl transferase inhibitor (FTI‑277) and geranylgeranyl transferase inhibitor (GGTI‑298), were used to investigate the effect on differentiation of keratinocytes (KCs). Western blotting demonstrated that PRA, ALD, FTI‑277 or GGTI‑298 alone, or in combination, inhibited the expression level of calcium‑induced differentiation maker involucrin (INV) in KCs. ALD and PRA induced greater inhibition of INV compared with FTI‑277 and GGTI‑298 treatment. These inhibitors additionally influenced the expression levels of keratin1. Mechanistic studies revealed that treatment of cells with inhibitors decreased the expression levels of p53 and Notch1, and regulated activation of the mitogen activated protein kinase and phosphoinositide‑3‑kinase/protein kinase B signaling pathways. The results of the present study suggested that regulation of the mevalonate pathway may be necessary for differentiation of KCs, and the pathogenesis of disseminated superficial actinic PK.

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October-2017
Volume 16 Issue 4

Print ISSN: 1791-2997
Online ISSN:1791-3004

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Spandidos Publications style
Jin R, Luo X, Luan K, Liu L, Sun LD, Yang S, Zhang SQ and Zhang XJ: Disorder of the mevalonate pathway inhibits calcium-induced differentiation of keratinocytes. Mol Med Rep 16: 4811-4816, 2017
APA
Jin, R., Luo, X., Luan, K., Liu, L., Sun, L., Yang, S. ... Zhang, X. (2017). Disorder of the mevalonate pathway inhibits calcium-induced differentiation of keratinocytes. Molecular Medicine Reports, 16, 4811-4816. https://doi.org/10.3892/mmr.2017.7128
MLA
Jin, R., Luo, X., Luan, K., Liu, L., Sun, L., Yang, S., Zhang, S., Zhang, X."Disorder of the mevalonate pathway inhibits calcium-induced differentiation of keratinocytes". Molecular Medicine Reports 16.4 (2017): 4811-4816.
Chicago
Jin, R., Luo, X., Luan, K., Liu, L., Sun, L., Yang, S., Zhang, S., Zhang, X."Disorder of the mevalonate pathway inhibits calcium-induced differentiation of keratinocytes". Molecular Medicine Reports 16, no. 4 (2017): 4811-4816. https://doi.org/10.3892/mmr.2017.7128