Modulation of human mesangial cell behaviour by extracellular matrix components—the possible role of interstitial type III collagen

Abstract

SUMMARYWe have investigated the effects of various cxtraeellular matrix (ECM) components on ihe behaviour of human mesangial ceils (HMC) in a gel culture system using a modified MTT assay methtxi. When cultured on a reconstituted basement membrane. Matrigcl (M gel). HMC aggregated and formed isolated colonies initially, then extended an array of cell processes to form a dendritic network structure and proliferated very slowly as the culture period progressed. On type I collagen gcKCl gel), however. HMC developed elongated bipolar sha|U's. migrated into the gel. and showed rapid cell growth. Next, separate ECM eompt>nents. sueh as type 111 and IV collagens. iaminin. heparin and heparan sulphate, were incorporated into Cl gel and HMC proliferation was assessed. Although attachmeni of HMC to each gel did not differ significantly. HMC proliferation was inhibited markedly on gels containing type III collagen, heparin and heparan sulphate; type IV collagen suppressed HMC proliferation slightly; and laminin had no signilicani effeei. These data suggest that interstiiial type I and III eollagcns. whieh are often observed in diseased glomeruli. as well as the basement membrane components, may play imporiani roles in the regulation of HMC proliferation under paihopliysiological conditions in vuo. We conclude that HMC behaviour is affected by the surrounding ECM constituents, whieh appear to function as a refined modulator.Keywords human mesangial cell extracellular matrix interstitial type III collagen gel culture modified MTT method

Pathophysiology of mesangial expansion in diabetic nephropathy: mesangial structure, glomerular biomechanics, and biochemical signaling and regulation

“…Rat mesangial cells cultured on collagen I matrix exhibited higher proliferation and migration rates than mesangial cells cultured on basement membrane matrix (Table 4 ) [ 69 ]. This behavior of rat mesangial cells has also been observed in human mesangial cells [ 70 ]. The increase in migration and proliferation rates indicate the activation of the mesangial cells, which is supported by mesangial cell elongation, another indicator of mesangial cell activation [ 69 , 70 ].…”

c-Myb regulates matrix metalloproteinases 1/9, and cathepsin D: implications for matrix-dependent breast cancer cell invasion and metastasis

“…We found that c-Myb does not activate cell invasion through the collagen I barrier. Modulation of cell invasion by ECM components was described previously [ 30 - 32 ]. Different invasion modes reflecting the specificity of substrates may be attributed to the different requirements on proteolytic systems [ 22 , 33 ].…”

The biology of immunoglobulin free light chains and kidney injury

“…127 Finally, ECM proteins may modulate MC function. 130,131 Thus, abnormal mesangium produced by MCs activated by FLCs may itself alter MC function and further potentiate glomerulosclerosis.…”