| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 3887916 | Kidney International | 2006 | 9 Pages |
The increased resistance of the glomerulus as a result of contractile dysfunction of mesangial cells (MCs) is associated with reduction of glomerular filtration rate and development of glomerulosclerosis. Evidences show MCs contraction changes with intracellular Ca2+ concentration ([Ca2+]i). Here, we explore the mechanism of angiotensin II (AngII)-induced Ca2+ oscillations and MCs contraction. Primary MCs from 3-month-old and 28-month-old rats were used for detection of Ca2+ oscillations and MC planar area with confocal microscopy. AngII could induce typical Ca2+ oscillations and contraction of MCs. This process was abolished by thapsigargin, 2-aminoethoxydiphenyl borate, or 1-O-octadecyl-2-O-methyl-sn-glycero-3-phosphorylcholine, and partially inhibited by ryanodine, but could not be inhibited in the absence of extracellular Ca2+. Ryanodine receptors (RyRs) and inositol 1,4,5-trisphosphate (InsP3) receptors displayed a strong colocalization, which may contribute to the amplification of Ca2+ response. MLC20 phosphorylation and MC planar area were associated with AngII-induced Ca2+ oscillations. The frequency of Ca2+ oscillations was dependent on the AngII concentration and correlated with the MCs' contractive extent, which could be attenuated by KN-93. The amplitude reduction of oscillations correlated with the decrease in aging-related contraction. In conclusion, [Ca2+]i response of MCs to AngII is characterized by repetitive spikes through the following repetitive cycles: Ca2+ release by phospholipase C –InsP3 pathway, Ca2+ amplification by Ca2+-activated RyRs and Ca2+ reuptake by the endoplasmic reticulum. MCs contraction can be modulated by oscillations not only in an AngII-induced frequency-dependent mode but also in an aging-related, amplitude-dependent mode.
