title: Continuous stretch-relaxation in culture alters rat mesangial cell morphology, growth characteristics, and metabolic activity.
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.
authors.affiliation: Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee.
authors.forename: R C
authors.initials: RC
authors.lastname: Harris
authors.forename: M A
authors.initials: MA
authors.lastname: Haralson
authors.forename: K F
authors.initials: KF
authors.lastname: Badr
mesh_terms: D000818:Animals; D002455:Cell Division; D002478:Cells, Cultured; D003094:Collagen / Q000096:biosynthesis; D003470:Culture Media; D015232:Dinoprostone / Q000096:biosynthesis; D005920:Glomerular Mesangium / Q000166:cytology* / Q000378:metabolism; D051381:Rats; D013314:Stress, Mechanical; D014618:Vacuum
chemical_list: D003470:Culture Media; D003094:Collagen; D015232:Dinoprostone