Showing papers by "Eric G. Neilson published in 1990"

Angiotensin II induces cellular hypertrophy in cultured murine proximal tubular cells

Abstract: In the present study we demonstrate that a murine proximal tubular cell line (MCT cells), expressing angiotensin II (ANG II) receptors [dissociation constant (Kd) = 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 transducible 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.

Cyclosporin A stimulates transcription and procollagen secretion in tubulointerstitial fibroblasts and proximal tubular cells.

Abstract: The brief study described in this report was undertaken to determine whether cyclosporin A had any direct effect on the expression of tubulointerstitial procollagens in cultured renal cells. Our findings indicate that murine tubulointerstitial fibroblasts secreted significantly more procollagen type I after the addition of cyclosporin A, whereas syngeneic proximal tubular cells expressed significantly more types I and IV procollagen after cyclosporin stimulation. These increases in procollagen gene product correlated concordantly with changes in the levels of cytoplasmic mRNA with procollagen-specific cDNA probes. Transfection of these fibroblasts and proximal tubular cells with chimeric gene constructs contaming enhancer/promoter elements for a2(I) and aI(IV) procollagen linked to a chloramphenicol acetyltransferase reporter gene indicates that the stimulatory effect of cyclosporin on procollagen expression depends, at least to some extent, on an increase in transcriptional activity.

Murine interstitial nephritis. IX. Induction of the nephritogenic effector T cell repertoire with an antigen-specific T cell cytokine.

Abstract: The experiments presented in this report describe the biochemical and functional characteristics of a soluble Th cell factor (ThF) which can induce a nephritogenic effector T cell repertoire producing autoimmune interstitial nephritis. The ThF is Ag-specific, I-A-restricted, and comprises two chains noncovalently linked as a heterodimer. One chain at approximately 78,000 Mr is related to the TCR/Id and expresses a framework determinant (14-30) common to Ag-binding factors, and the other chain at approximately 82,000 Mr is I-A+. Together these chains can replace their parent cell by providing cognate help to precursor effector T lymphocytes in the presence of accessory cells, tubular Ag, and IL-2.