Angiotensin II induces cellular hypertrophy in cultured murine proximal tubular cells

Gunter Wolf, Eric G. Neilson*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

227 Scopus citations

Abstract

In the present study we demonstrate that a murine proximal tubular cell line (MCT cells), expressing angiotensin II (ANG II) receptors [dissociation constant (K(d)) = 0.89 nM; receptor density (R0) = 46,900 receptors/cell] in culture, can be induced to hypertrophy after the daily addition of exogenous ANG II (10-8 M). This hypertrophic response was characterized by an increase in total cellular protein content, by an enhancement of [3H]leucine incorporation into precipitable proteins, and by an augmentation in cell size by cytofluorography. This ANG II effect producing MCT cell enlargement was demonstrable in the absence of cellular proliferation. Proliferation of MCT cells, however, could be induced by epidermal growth factor (EGF) or platelet-derived growth factor (PDGF), and pretreatment of rested MCT cells with ANG II further enhanced EGF-induced cell division. ANG II-induced hypertrophy in MCT cells was factor specific, in that it could be blocked with saralasin, and not induced by angiotensin I (ANG I). This hypertrophic response was also independent of prostaglandin E2 synthesis but was transducable by pertussis toxin-sensitive G proteins and involved, to some extent, the activation of Na+-H+ exchange. ANG II, as well as EGF and/or PDGF, moreover, could induce the cellular oncogenes c-fos, c-myc, c-N-ras, but not c-cis, which suggests that early gene activation is probably not a specific prerequisite for hypertrophy. Our findings demonstrate that ANG II, in culture, can be a single-factor event capable of inducing hypertrophy in proximal tubular cells.

Original languageEnglish (US)
Pages (from-to)F768-F777
JournalAmerican Journal of Physiology - Renal Fluid and Electrolyte Physiology
Volume259
Issue number5 28-5
DOIs
StatePublished - 1990

Keywords

  • Oncogene expression
  • Procollagen
  • Signal transduction
  • Sodium ion-hydrogen ion exchange

ASJC Scopus subject areas

  • Physiology

Fingerprint Dive into the research topics of 'Angiotensin II induces cellular hypertrophy in cultured murine proximal tubular cells'. Together they form a unique fingerprint.

Cite this