Mesangial medium with IgA1 from IgA nephropathy inhibits nephrin expression in mouse podocytes.
BACKGROUND
IgA nephropathy (IgAN) is characterized by mesangial deposition of polymeric IgA1, and podocyte injury plays an important role in glomerulosclerosis of the disease. Our previous study indicated that medium of mesangial cells co-incubated with aggregated IgA1 (aIgA1), isolated from IgAN patients, down-regulated nephrin expression. Yet the mechanism remains unclear.


METHODS
Podocytes were incubated with a medium of mesangial cells co-incubated with aIgA1, which was isolated from IgAN patients, and enalaprilat (10(-5) M), valsartan (10(-5) M) and anti-mouse tumour necrosis factor-alpha antibody (50 ng mL(-1)) separately. Nephrin expression in podocytes was measured by real-time polymerase chain reaction and Western blot analysis.


RESULTS
The level of angiotensinogen and angiotensin-converting enzyme mRNAs in podocytes, as well as angiotensin, was also increased by a medium of mesangial cells co-incubated with aIgA1 from IgAN patients (P<0.05). Enalaprilat or valsartan partly improved nephrin expression when compared with that by podocytes exposed to the mesangial medium (P<0.05), while the nephrin expression of podocytes with enalaprilat or valsartan was lower than that of podocytes exposed to medium of mesangial cells stimulated by aIgA1 from healthy control (P<0.05). However, anti-mouse tumour necrosis factor-alpha antibody did not show any improvement in nephrin expression.


CONCLUSIONS
Our findings implicate that local renin angiotensin system activation in podocytes is partly involved in down-regulation of nephrin by mesangial medium in IgA nephropathy.
Wang
C
C
Department of nephrology,The 3rd affiliated hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China.
Liu
X
X
Ye
Z
Z
Zhang
J
J
Tang
H
H
Chen
Z
Z
Zhang
H
H
Lou
T
T
D000818:Animals; D002478:Cells, Cultured / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects; D015870:Gene Expression / Q000187:drug effects; D005922:Glomerulonephritis, IGA / Q000235:genetics / Q000473:pathology*; D006801:Humans; D007070:Immunoglobulin A / Q000235:genetics / Q000378:metabolism*; D008565:Membrane Proteins / Q000187:drug effects / Q000378:metabolism*; D050527:Mesangial Cells / Q000378:metabolism*; D051379:Mice; D050199:Podocytes / Q000378:metabolism*; D012016:Reference Values; D012084:Renin-Angiotensin System / Q000187:drug effects* / Q000235:genetics
D007070:Immunoglobulin A; D008565:Membrane Proteins; C113267:nephrin