739 research outputs found
Serum Amyloid P Inhibits Fibrosis through Fc Gamma R-Dependent Monocyte- Macrophage Regulation in Vivo (Vol 1, 5ra13, 2009)
No full textsj-docx-1-taj-10.1177_20406223231177291 – Supplemental material for Predialysis trajectories of estimated GFR and concurrent trends of Chronic Kidney Disease-relevant biomarkers
No full textSupplemental material, sj-docx-1-taj-10.1177_20406223231177291 for Predialysis trajectories of estimated GFR and concurrent trends of Chronic Kidney Disease-relevant biomarkers by Hsiao-Mei Tsao, Tai-Shuan Lai, Yu-Hsiang Chou, Shuei-Liong Lin and Yung-Ming Chen in Therapeutic Advances in Chronic Disease</p
Pentoxifylline Inhibits Platelet-Derived Growth Factor-Stimulated Cyclin D1 Expression in Mesangial Cells by Blocking Akt Membrane Translocation
No full textPentoxifylline (PTX) is a potent inhibitor of mesangial cell pro-liferation,
but its underlying mechanism is poorly understood.
Here, we demonstrate that in platelet-derived growth factor
(PDGF)-stimulated mesangial cells, PTX causes G1 arrest by
down-regulation of cyclin D1 expression, which subsequently
attenuates Cdk4 activity. In vivo, PTX similarly reduces cyclin
D1 expression in mesangial cells of rats with acute Thy1 glo-merulonephritis.
The mechanism by which PTX reduces cyclin
D1 is also investigated. PTX blocks Akt but not phosphatidyl-inositol
3-kinase (PI3K) activation in response to PDGF and
abrogates cyclin D1 induction by PI3K, suggesting an effect of
PTX on Akt itself. Indeed, PTX is capable of blocking the
membrane translocation of Akt, and enforced targeting of Akt
to cell membrane prevents the inhibition of Akt and cyclin D1 by
PTX. Because PTX is known to increase intracellular cAMP
levels by inhibiting phosphodiesterase, the role of protein ki-nase
A (PKA) in these events is investigated. The PKA antago-nist
N-[2-(4-bromocinnamylamino)ethyl]-5-isoquinoline (H89)
abolishes cell proliferation effects of PTX and restores cyclin D1
expression as well as Akt membrane translocation and activa-tion
by PDGF, whereas dibutyryl cAMP and forskolin recapitu-late
the functions of PTX in mesangial cells. In conclusion, our
results indicate that PTX, acting through PKA, interferes with
PDGF signaling to Akt activation by blocking Akt membrane
translocation, thereby inhibiting cyclin D1 expression and mes-angial
cell proliferation
Outcomes of Stage 3-5 Chronic Kidney Disease before End-Stage Renal Disease at a Single Center in Taiwan
No full textEffect of Pentoxifylline in Addition to Losartan on Proteinuria and GFR in CKD：A 12-month Randomized Trial
No full textPericytes and Perivascular Fibroblasts Are the Primary Source of Collagen- Producing Cells in Obstructive Fibrosis of the Kidney
No full textUnderstanding the origin of scar-producing myofibroblasts is vital in discerning the mechanisms by which fibrosis develops in response to inflammatory injury. Using a transgenic reporter mouse model expressing enhanced green fluorescent protein (GFP) under the regulation of the collagen type I, 1 (coll1a1) promoter and enhancers, we examined the origins of coll1a1-producing cells in the kidney. Here we show that in normal kidney, both podocytes and pericytes generate coll1a1 transcripts as detected by enhanced GFP, and that in fibrotic kidney, coll1a1-GFP expression accurately identifies myofibroblasts. To determine the contribution of circulating immune cells directly to scar production, wild -type mice, chimeric with bone marrow from coll-GFP mice, underwent ureteral obstruction to induce fibrosis. Histological examination of kidneys from these mice showed recruitment of small numbers of fibrocytes to the fibrotic kidney, but these fibrocytes made no significant contribution to interstitial fibrosis. Instead, using kinetic modeling and time course microscopy, we identified coll1a1-GFP-expressing pericytes as the major source of interstitial myofibroblasts in the fibrotic kidney . Our studies suggest that either vascular injury or vascular factors are the most likely triggers for pericyte migration and differentiation into myofibroblasts. Therefore , our results serve to refocus fibrosis research to injury of the vasculature rather than injury to the epithelium
Pentoxifylline Inhibits Platelet-Derived Growth Factor-Stimulated Cyclin D1 Expression in Mesangial Cells by Blocking Akt Membrane Translocation
No full text- …
