Inhibition of renin/prorenin receptor attenuated mesangial cell proliferation and reduced associated fibrotic factor release.
The present study was designed to investigate the physiological roles of renin/prorenin receptor in cultured rat mesangial cells. The presence of renin/prorenin receptor in mesangial cells was determined by immunofluorescence staining, real-time quantitative reverse transcriptase-polymerase chain reaction (real-time PCR) and Western blotting assay. The expression of renin/prorenin receptors was identified in both rat renal slices and cultured mesangial cells. Meanwhile, the cultured mesangial cells were demonstrated synthesizing and secreting (Pro)renin as well. Knockdown of renin/prorenin receptor expression was performed by small interfering RNA (siRNA) transfection. Either knockdown or blockade of renin/prorenin receptor by handle region peptide (HRP) reduced mesangial cell proliferation. In the meantime, release of type IV collagen, phosphorylation of extracellular signal-regulated kinases 1 and 2 (ERK1/2) and mRNA level of transforming growth factor-beta1 (TGF-beta1) were decreased. On the other hand, both the production and activity of matrix metalloproteinase-2, a key enzyme to degrade type IV collagen, was increased. The present results indicated that renin/prorenin receptor played a regulatory role in mesangial cells proliferation and extracellular matrix accumulation. Blockade of renin/prorenin receptors may postpone over extracellular accumulation, which occurs in some pathological situations, via suppressed both mesangial cell proliferation and fibrotic factor release.
He
Ming
M
Department of Physiology and Pathophysiology, Shanghai Medical College, Fudan University, Shanghai, People's Republic of China.
Zhang
Lin
L
Shao
Ying
Y
Wang
Xiaofang
X
Huang
Yu
Y
Yao
Tai
T
Lu
Limin
L
D000595:Amino Acid Sequence; D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D003094:Collagen / Q000378:metabolism; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005355:Fibrosis / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D055785:Gene Knockdown Techniques; D007668:Kidney / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D050527:Mesangial Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D009842:Oligopeptides / Q000737:chemistry / Q000494:pharmacology; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011956:Receptors, Cell Surface / Q000172:deficiency* / Q000378:metabolism*; D053773:Transforming Growth Factor beta1 / Q000235:genetics; D000093342:Prorenin Receptor
D009842:Oligopeptides; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D053773:Transforming Growth Factor beta1; C527127:handle-region peptide, rat; D003094:Collagen; D048049:Extracellular Signal-Regulated MAP Kinases; D020778:Matrix Metalloproteinase 2; C522363:Mmp2 protein, rat; D000093342:Prorenin Receptor