Recombinant tissue factor pathway inhibitor induces apoptosis in cultured rat mesangial cells via its Kunitz-3 domain and C-terminal through inhibiting PI3-kinase/Akt pathway

Yi Feng Lin, Nong Zhang, Hong Shen Guo, De Sheng Kong, Tao Jiang, Wang Liang, Zhong Hua Zhao, Qi Qun Tang, Duan Ma

Research output: Contribution to journalArticlepeer-review

Abstract

Tissue factor pathway inhibitor (TFPI) is an endogenous inhibitor of tissue factor (TF) induced coagulation. In addition to its anticoagulation activity, TFPI has other functions such as antiproliferation and inducing apoptosis. In the present study, we investigated whether or not TFPI induced apoptosis in cultured rat mesangial cells (MsCs) and the possible signal pathway that involved in the apoptotic process. We demonstrated that recombinant TFPI (rTFPI) induced apoptosis in cultured MsCs via its Kunitz-3 domain and C-terminal in a dose- and time-dependent manner by Hoechst 33258 assay, flow cytometry, nucleosomal laddering of DNA, caspase 3 assay. Because the serine/threonine protein kinase Akt has attracted attention as a mediator of survival (anti-apoptotic) signal in MsCs, we investigated the expression of phosphospecific-Akt and its downstream signal phospho-IκB-α and some other signal molecules like Fas and bcl-2. The results indicated that the process of apoptosis triggered by rTFPI is, at least in part, actively conducted by rat MsCs possibly through PI3-Kinase-Akt signal pathway not by binding to tissue factor. Our findings suggest that rTFPI has the potential usefulness in inducing apoptosis of MsCs under inflammatory conditions.

Original languageEnglish (US)
Pages (from-to)2163-2173
Number of pages11
JournalApoptosis
Volume12
Issue number12
DOIs
StatePublished - Dec 2007
Externally publishedYes

Keywords

  • Apoptosis
  • Mesangial cell
  • PI3-kinase/Akt pathway
  • Recombinant tissue factor pathway inhibitor

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Cell Biology

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