Nicotine inhibits murine Leydig cell differentiation and maturation via regulating Hedgehog signal pathway

Jiajie Wu, Wangjie Xu, Dong Zhang, Jingbo Dai, Yong Cao, Yilin Xie, Lianyun Wang, Zhiguang Qiao*, Zhongdong Qiao

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

Abstract

Nicotine, the main toxic substance in cigarette smoke, significantly reduced the differentiation and maturation ratio of Leydig cell in murine testes. To investigate the underlying mechanism, C57BL/6J mice were divided into control (CT) and nicotine treated (NT) groups. Next generation RNA sequencing and bio-informatics analysis were carried out to analysis the effects of nicotine on the RNA profile of Leydig cells. Expression level of 7 pathways remarkably changed after nicotine treatment. As the positive regulating pathway of Leydig cell differentiation, Hedgehog signaling pathway was found among these pathways. PTCH1 and β-TrCP were down-regulated in nicotine treated mice Leydig cells, while GSK3β Gli2 and Gli2 fragments increased significantly. Nicotine stimulated the destabilization of Gli2 via β-TrCP induced ubiquitination and degradation. Gli2 was phosphorylated by up-expressed GSK3β during this process. Destabilization of Gli2 reduced the activation rate of target genes of Hedgehog signaling pathway such as Ptch1. The differentiation of Leydig cell positively regulated by Hh pathway was thus inhibited by nicotine exposure. Consequently, the male reproduction process powered by Leydic cell-mediated androgen secretion was thus influenced. In conclusion, we find that nicotine inhibits murine Leydig cell differentiation and maturation via regulating Hedgehog signal pathway.

Original languageEnglish (US)
Pages (from-to)1-7
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume510
Issue number1
DOIs
StatePublished - Feb 26 2019

Keywords

  • Differentiation
  • Gli2 destabilization
  • Hedgehog signaling pathway
  • Leydig cell
  • Maturation
  • Nicotine

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

Fingerprint

Dive into the research topics of 'Nicotine inhibits murine Leydig cell differentiation and maturation via regulating Hedgehog signal pathway'. Together they form a unique fingerprint.

Cite this