NHERF-2 maintains endothelial homeostasis

Resham Bhattacharya, Enfeng Wang, Shamit K. Dutta, Pawan K. Vohra, E. Guangqi, Y.s. Prakash, Debabrata Mukhopadhyay

Research output: Contribution to journalArticle

8 Scopus citations

Abstract

The Na +/H + exchanger regulatory factor-2 (NHERF-2) is an integral component of almost all endothelial cells (ECs), yet its endothelial function is not known. Here, we found that NHERF-2, is a key regulator of endothelial homeostasis because NHERF-2-silenced ECs proliferate at a much higher rate even in the absence of mitogens such as VEGF compared with control ECs. We further show that the hyperproliferation phenotype of NHERF-2-silenced EC is because of an accelerated cell cycle that is probably caused by a combination of the following factors: increased cytoplasmic calcium, increased expression of c-Myc, increased expression of cyclin D1, and reduced expression of p27. Using an experimental mouse model of human hemangioma, we found that the endothelial neoplasms derived from NHERF-2-silenced cells were much larger in volume than those derived from control cells. Thus, NHERF-2 is a negative regulator of endothelial proliferation and may have important roles in endothelial homeostasis and vascular modeling.

Original languageEnglish (US)
Pages (from-to)4798-4806
Number of pages9
JournalBlood
Volume119
Issue number20
DOIs
StatePublished - May 17 2012

    Fingerprint

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

Cite this

Bhattacharya, R., Wang, E., Dutta, S. K., Vohra, P. K., Guangqi, E., Prakash, Y. S., & Mukhopadhyay, D. (2012). NHERF-2 maintains endothelial homeostasis. Blood, 119(20), 4798-4806. https://doi.org/10.1182/blood-2011-11-392563