Effects Of SPARC And Its Peptide On Proliferation And Apoptosis Of Human Mesangial Cells Cultured In Vitro

Objective To investigate the effects of secreted protein acidic and rich in cysteine (SPARC) and its peptide on proliferation and the expression of extracellular matrix of human mesangial cells (HMC) cultured in vitro. Methods MTT, Annexin V/PI binding, RT-PCR, FCM, Electron microscope, Immunocytochemistry, Immunohistochemistry, ELISA and Western blot analysis were applied in present study. Results SPARC and its peptide could significantly inhibit the proliferation of HMC with dose- and time-dependent pattern, regulate the cell cycle at phrase G0/G1 increased while cells phrase S reduced, and could also induce apoptosis. Under the stimulation of SPARC and its peptide, the expression of CyclinD1 in HMC decreased, the expression of P21^Wafl mRNA increased significantly, the expression of collagen type I, collagen type IV, and fibronectin mRNA were down-regulated. The SPARC levels in the serum and urine of patients with IgA nephropathy were higher than that in the controls. The serum levels of TNF-α, IL-1βand IL-6 in IgAN group were elevated than those in control group, while the levels in urinary TNF-αand IL-6 in IgAN group were also higher than those of controls. SPARC was weakly expressed in normal cortical distal tubules. In renal tissues from patients with IgA nephropathy, SPARC was mainly localized to tubular epithelial cells, and strongly positive staining was found in cytoplasm. Conclusions SPARC and its peptide can effectively inhibit HMC proliferation and regulate cell cycle progression, which will be useful for treating mesangial proliferative glomerulonephritis.