Mesangial Cells Stimulated by Immunoglobin A1 from IgA Nephropathy Upregulates Transforming Growth Factor-β1 Synthesis in Podocytes Via Renin-Angiotensin System Activation

Abstract

We undertook this study to investigate the effect of mesangial cells stimulated by immunoglobin A1 from IgAN on transforming growth factor-beta1 synthesis in podocytes. Jacalin affinity chromatography and Sephacryl S-200 molecular sieve chromatography were used to isolate IgA1 from blood of IgAN patients, which was then used as aggregated IgA1 (aIgA1). Podocytes were incubated with special mesangial medium. Real-time polymerase chain reaction (PCR) and enzyme-linked immunosorbent assay (ELISA) were used, respectively, to measure TGF-beta1 mRNA expression and its protein concentration in medium. TGF-beta1 mRNA and its protein concentration in the medium of podocytes increased when exposed to the medium of mesangial cells, which were stimulated by IgA1 from IgAN patients. Angiotensinogen and angiotensin-converting enzyme (ACE) mRNAs, as well as angiotensin II, were also increased by the medium (p <0.05). Enalaprilat and valsartan partly lowered overproduction of TGF-beta1 mRNA and excreted protein of podocytes, whereas enalaprilat plus valsartan completely restored them to the level as control. These data suggest that mesangial cells stimulated by IgA1 from IgAN patients may excrete some material to facilitate TGF-beta1 synthesis in podocytes through activating renin-angiotensin system by cross-talk.