scholarly journals Specific Inhibitor of Smad3 (SIS3) Attenuates Fibrosis, Apoptosis, and Inflammation in Unilateral Ureteral Obstruction Kidneys by Inhibition of Transforming Growth Factor β (TGF-β)/Smad3 Signaling

2018 ◽  
Vol 24 ◽  
pp. 1633-1641 ◽  
Author(s):  
Xingli Ji ◽  
Honglian Wang ◽  
Zhaojun Wu ◽  
Xia Zhong ◽  
Menglian Zhu ◽  
...  
Keyword(s):  
Growth Factor ◽  
Ureteral Obstruction ◽  
Transforming Growth Factor ◽  
Specific Inhibitor ◽  
Transforming Growth Factor Β ◽  
Unilateral Ureteral Obstruction ◽  
Apoptosis And Inflammation

scholarly journals Antibody to transforming growth factor-β ameliorates tubular apoptosis in unilateral ureteral obstruction

2000 ◽  
Vol 58 (6) ◽  
pp. 2301-2313 ◽  
Author(s):  
Akira Miyajima ◽  
Jie Chen ◽  
Cathy Lawrence ◽  
Steve Ledbetter ◽  
Robert A. Soslow ◽  
...  
Keyword(s):  
Growth Factor ◽  
Ureteral Obstruction ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Unilateral Ureteral Obstruction

scholarly journals UT-A1/A3 knockout mice show reduced fibrosis following unilateral ureteral obstruction

2020 ◽  
Vol 318 (5) ◽  
pp. F1160-F1166
Author(s):  
Fitra Rianto ◽  
Akihiro Kuma ◽  
Carla L. Ellis ◽  
Faten Hassounah ◽  
Eva L. Rodriguez ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Growth Factor ◽  
Kidney Disease ◽  
Knockout Mice ◽  
Ureteral Obstruction ◽  
Renal Fibrosis ◽  
Transforming Growth Factor ◽  
Smooth Muscle Actin ◽  
Transforming Growth Factor Β ◽  
Unilateral Ureteral Obstruction

Renal fibrosis is a major contributor to the development and progression of chronic kidney disease. A low-protein diet can reduce the progression of chronic kidney disease and reduce the development of renal fibrosis, although the mechanism is not well understood. Urea reabsorption into the inner medulla is regulated by inner medullary urea transporter (UT)-A1 and UT-A3. Inhibition or knockout of UT-A1/A3 will reduce interstitial urea accumulation, which may be beneficial in reducing renal fibrosis. To test this hypothesis, the effect of unilateral ureteral obstruction (UUO) was compared in wild-type (WT) and UT-A1/A3 knockout mice. UUO causes increased extracellular matrix associated with increases in transforming growth factor-β, vimentin, and α-smooth muscle actin (α-SMA). In WT mice, UUO increased the abundance of three markers of fibrosis: transforming growth factor-β, vimentin, and α-SMA. In contrast, in UT-A1/A3 knockout mice, the increase following UUO was significantly reduced. Consistent with the Western blot results, immunohistochemical staining showed that the levels of vimentin and α-SMA were increased in WT mice with UUO and that the increase was reduced in UT-A1/A3 knockout mice with UUO. Masson’s trichrome staining showed increased collagen in WT mice with UUO, which was reduced in UT-A1/A3 knockout mice with UUO. We conclude that reduced UT activity reduces the severity of renal fibrosis following UUO.

scholarly journals INK4a knockout mice exhibit increased fibrosis under normal conditions and in response to unilateral ureteral obstruction

2010 ◽  
Vol 299 (6) ◽  
pp. F1486-F1495 ◽  
Author(s):  
Jesse M. Wolstein ◽  
David H. Lee ◽  
Jennine Michaud ◽  
Venessa Buot ◽  
Beth Stefanchik ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Knockout Mice ◽  
Ureteral Obstruction ◽  
Transforming Growth Factor ◽  
Mesangial Cells ◽  
Collecting Duct ◽  
Mesenchymal Cell ◽  
Transforming Growth Factor Β ◽  
Unilateral Ureteral Obstruction ◽  
Matrix Deposition

The INK4a proteins p16INK4a and p19ARF regulate cell cycle arrest and senescence. However, the role of these proteins in controlling these processes in the normal kidney and following injury is unknown. We performed unilateral ureteral obstruction (UUO) to induce fibrosis in 2- to 3-mo-old wild-type (WT) C57/B6 and INK4a knockout mice. By quantitative RT-PCR, p16INK4a levels were increased sixfold in WT mice 7 days after UUO and p19ARF remained undetectable. Kidney sections were examined to determine levels and localization of p16INK4a, apoptosis, fibrosis, and senescent cells. INK4a knockout mice displayed mesangial cell proliferation, increased matrix deposition, and myofibroblast differentiation under normal conditions. Following UUO, INK4a knockout mice displayed 10-fold increased tubular and interstitial cell proliferation, 75% decreased collecting duct apoptosis, 2-fold greater collagen and fibronectin deposition, and no cell senescence by senescence-associated β-galactosidase staining compared with WT mice. Both INK4a knockout mesangial cells and kidney lysates from knockout mice following injury showed elevated levels of IL-6 by ELISA compared with WT samples. INK4a knockout epithelial cell cultures displayed increased mesenchymal cell markers when exposed to transforming growth factor-β. These results confirm that p16INK4a controls cell proliferation and matrix production and mitigates fibrosis following injury and suggest that the mechanism involves a role in limiting inflammation and cell proliferation.

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