Homeodomain-interacting protein kinase2 in human idiopathic pulmonary fibrosis

Alberto Ricci, Emanuela Cherubini, Alessandra Ulivieri, Luca Lavra, Salvatore Sciacchitano, Davide Scozzi, Rita Mancini, Gennaro Ciliberto, Armando Bartolazzi, Pierdonato Bruno, Paolo Graziano, Salvatore Mariotta

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Abstract

Homeodomain-interacting protein kinase 2 (Hipk2) is an emerging player in cell response to genotoxic agents that contributes to the cell's decision between cell cycle arrest or apoptosis. HIPK2 acts as co-regulator of an increasing number of transcription factors and modulates many different basic cellular processes such as apoptosis, proliferation, DNA damage response, differentiation. Idiopathic pulmonary fibrosis (IPF) is characterized by an anatomical disarrangement of the lung due to fibroblast proliferation, extracellular matrix deposition and lung function impairment. Although the role of inflammation is still debated, attention has been focused on lung cell functions as fibroblast phenotype and activity. Aim of the present study was to analyze the loss of heterozygosity (LOH) at HIPK2 locus 7q32.34 in human lung fibroblasts and the HIPK2 expression in 15 IPF samples and in four primary fibroblast cell cultures isolated from IPF biopsies using semi-quantitative RT-PCR, Western blots and immunohistochemistry. We demonstrated a frequency of LOH in IPF fibroblasts of 46% for the internal D7S6440 microsatellite and 26.6% for the external D7S2468 microsatellite. Furthermore, we demonstrated low HIPK2 protein expression in those fibroblasts from IPF patients that present the HIPK2 LOH. The restoration of HIPK2 expression in IPF derived cells induced a significant reduction of chemoresistance after treatment with cisplatin. The results obtained allow us to hypothesize that HIPK2 dysfunction may play a role in fibroblasts behavior and in IPF pathogenesis. HIPK2 may be considered as a novel potential target for anti-fibrosis therapy.

Original languageEnglish
Pages (from-to)235-241
Number of pages7
JournalJournal of Cellular Physiology
Volume228
Issue number1
DOIs
Publication statusPublished - Jan 2013

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ASJC Scopus subject areas

  • Clinical Biochemistry
  • Cell Biology
  • Physiology

Cite this

Ricci, A., Cherubini, E., Ulivieri, A., Lavra, L., Sciacchitano, S., Scozzi, D., Mancini, R., Ciliberto, G., Bartolazzi, A., Bruno, P., Graziano, P., & Mariotta, S. (2013). Homeodomain-interacting protein kinase2 in human idiopathic pulmonary fibrosis. Journal of Cellular Physiology, 228(1), 235-241. https://doi.org/10.1002/jcp.24129