Mesangial cells in diabetic mice and human kidneys with diabetic nephropathy exhibit increased type VIII collagen, a nonfibrillar protein that exists as a heterodimer composed of α1(VIII) and α2(VIII), encoded by Col8a1 and Col8a2, respectively. Because TGF-β1 promotes the development of diabetic glomerulosclerosis, we studied whether type VIII collagen modulates the effects of TGF-β1 in mesang...

In view of its proven antiproliferative effects, rapamycin offers potential in the treatment of mesangioproliferative disease. Previous data have shown an effect of rapamycin on mesangial cell proliferation at high doses and have not explored the mechanism of action. Therefore, we explored the effects and mechanism of action of low levels of rapamycin on mesangial cell proliferation. Primary cu...

BACKGROUND/AIMS IFN-γ-inducible protein 10 (IP-10, CXCL10) has been widely demonstrated to be involved in chemotaxis, cell growth regulation and angiogenesis inhibition. It has been reported that CXCL10 expression is significantly increased in patients with MesPGN (Mesangial proliferative glomerulonephritis). However, the underlying mechanism of CXCL10 in MesPGN reminds unclear. METHODS Wildt...

Mesangial cell proliferation and matrix overproduction characterize many progressive glomerular diseases. Based on currently available data, the role of interleukin-6 (IL-6) in mediating mesangial cell proliferation and matrix production is controversial. The present study attempts to clarify this issue by showing that: (1) IL-6 knock out mice develop a normal glomerular architecture and in par...

Diabetic nephropathy (DN) is one of the most common complications diabetes, and its main manifestations are progressive proteinuria abnormal renal function, which eventually develops end stage disease (ESRD). The pathogenesis DN complex involves many signaling pathways molecules, including metabolic disorders, genetic factors, oxidative stress, inflammation, microcirculatory abnormalities strat...

The potent vasoconstrictor arginine vasopressin (AVP) is also a mitogen for mesangial cells. Treatment with AVP decreased transit time through the cell cycle. AVP-stimulated mesangial cell growth by activating both the Ras mitogen-activated protein kinase (MAPK) and the phosphatidylinositol 3-kinase (PI3K) cell signaling pathways. Both the selective PI3K inhibitor LY-294002 and the MAPK kinase ...

Schnaper, H. William, Tomoko Hayashida, Susan C. Hubchak, and Anne-Christine Poncelet. TGFsignal transduction and mesangial cell fibrogenesis. Am J Physiol Renal Physiol 284: F243–F252, 2003; 10.1152/ajprenal.00300.2002.—Transforming growth factor(TGF) is closely associated with progressive renal fibrosis. Significant progress has been accomplished in determining the cellular signaling pathways...

To elucidate physiological and clinical implications of the natriuretic peptide family, the expression of receptors for natriuretic peptides has been examined in cultured cells (a rat pheochromocytoma cell line [PC12], bovine endothelial cells, rat aortic smooth muscle cells, human mesangial cells, and a porcine kidney epithelial cell line [LLC-PK1]) by Northern blot analysis and cyclic GMP pro...

Mesangial cells organize the glomerular capillaries by adhering to the G domain of laminin alpha5 in the glomerular basement membrane. n developing glomeruli, laminin ␣ 5 replaces laminin ␣ 1 in the glomerular basement membrane (GBM) at the capillary loop stage, a transition required for glomerulogenesis. To investigate domain-specific functions of laminin ␣ 5 during glomerulogenesis, we produc...