Continuous stretch-relaxation in culture alters rat mesangial cell morphology, growth characteristics, and metabolic activity

Lab Invest. 1992 May;66(5):548-54.

Abstract

Mesangial cells serve many functions in the glomerulus, including regulation of glomerular ultrafiltration coefficient, matrix production, and eicosanoid generation. The glomerulus is a vascular bed, and the mesangial cell is continually exposed to rhythmic alterations in intraglomerular pressure. Since increased intraglomerular pressure has been implicated as a potential causative agent in the ultimate development of nephrosclerosis, we sought to determine the effect of continuous stretch-relaxation upon parameters of mesangial cell growth and function. Early passage (2-4) cultured rat mesangial cells were plated onto either rigid-bottom or flexible-bottom culture plates coated with type I collagen. After cell attachment, the cells on flexible supports were exposed to continuous stretch-relaxation for 72 to 96 hours at a rate of 100 cycles/minutes at an applied pressure of 7 to 8 KPa (53 to 61 mm Hg). Cellular morphology was altered by continuous stretch-relaxation, with the majority of mesangial cells presenting stellate or straplike morphology. Fluorescein isothiocyanate-labeled phalloidin staining indicated an increase in density of actin filaments running the long axis of the cell. Stretch-relaxation resulted in an approximately 50% increase in cell number. Prostaglandin production, assessed as irPGE2 production, was increased by stretching in mesangial cells from 28 +/- 1 to 49 +/- 4 pg/10(6) cells (N = 12; p less than 0.005). Mechanical stretch/relaxation increased the percentage of protein representing collagenous proteins from 47 +/- 6% to 70 +/- 4%, as assessed by collagenase susceptibility (p less than 0.025). Analysis of pepsin-resistant proteins synthesized indicated that stretch/relaxation resulted in increases in the relative amounts of types I and III collagens produced/cell. Additionally, stretch/relaxation selectively increased the relative amount of type I-homotrimers produced. Thus, when mesangial cells are exposed to cyclic stretch/relaxation, they exhibit significant alterations in morphology, growth, prostaglandin and collagen production.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Cell Division
  • Cells, Cultured
  • Collagen / biosynthesis
  • Culture Media
  • Dinoprostone / biosynthesis
  • Glomerular Mesangium / cytology*
  • Glomerular Mesangium / metabolism
  • Rats
  • Stress, Mechanical
  • Vacuum

Substances

  • Culture Media
  • Collagen
  • Dinoprostone