scholarly journals Canonical Transforming Growth Factor-β Signaling Regulates Disintegrin Metalloprotease Expression in Experimental Renal Fibrosis via miR-29

2013 ◽  
Vol 183 (6) ◽  
pp. 1885-1896 ◽  
Author(s):  
Vasudev Ramdas ◽  
Martin McBride ◽  
Laura Denby ◽  
Andrew H. Baker
Keyword(s):  
Growth Factor ◽  
Renal Fibrosis ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β

scholarly journals Dimethylfumarate Attenuates Renal Fibrosis via NF-E2-Related Factor 2-Mediated Inhibition of Transforming Growth Factor-β/Smad Signaling

PLoS ONE ◽  
2012 ◽  
Vol 7 (10) ◽  
pp. e45870 ◽  
Author(s):  
Chang Joo Oh ◽  
Joon-Young Kim ◽  
Young-Keun Choi ◽  
Han-Jong Kim ◽  
Ji-Yun Jeong ◽  
...  
Keyword(s):  
Growth Factor ◽  
Renal Fibrosis ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Related Factor ◽  
Smad Signaling

TGF-β and CTGF have overlapping and distinct fibrogenic effects on human renal cells

2002 ◽  
Vol 283 (4) ◽  
pp. F707-F716 ◽  
Author(s):  
Elizabeth Gore-Hyer ◽  
Daniel Shegogue ◽  
Malgorzata Markiewicz ◽  
Shianlen Lo ◽  
Debra Hazen-Martin ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Growth Factors ◽  
Growth Factor ◽  
Renal Fibrosis ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Tissue Growth ◽  
Mrna Levels ◽  
Potent Inducer ◽  
Collagen Promoter

Transforming growth factor-β (TGF-β) and connective tissue growth factor (CTGF) are ubiquitously expressed in various forms of tissue fibrosis, including fibrotic diseases of the kidney. To clarify the common and divergent roles of these growth factors in the cells responsible for pathological extracellular matrix (ECM) deposition in renal fibrosis, the effects of TGF-β and CTGF on ECM expression in primary human mesangial (HMCs) and human proximal tubule epithelial cells (HTECs) were studied. Both TGF-β and CTGF significantly induced collagen protein expression with similar potency in HMCs. Additionally, α2(I)-collagen promoter activity and mRNA levels were similarly induced by TGF-β and CTGF in HMCs. However, only TGF-β stimulated collagenous protein synthesis in HTECs. HTEC expression of tenascin-C (TN-C) was increased by TGF-β and CTGF, although TGF-β was the more potent inducer. Thus both growth factors elicit similar profibrogenic effects on ECM production in HMCs, while promoting divergent effects in HTECs. CTGF induction of TN-C, a marker of epithelial-mesenchymal transdifferentiation (EMT), with no significant induction of collagenous protein synthesis in HTECs, may suggest a more predominant role for CTGF in EMT rather than induction of excessive collagen deposition by HTECs during renal fibrosis.

scholarly journals Role of Transcription Factors and Growth Factors in Renal Fibrosis in Felines with Kidney Dysfunction

2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 1532-1532
Author(s):  
Kiran Panickar ◽  
Selena Tavener ◽  
Dennis Jewell
Keyword(s):  
Growth Factor ◽  
Kidney Disease ◽  
Renal Fibrosis ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Nutritional Therapy ◽  
Kidney Dysfunction ◽  
Funding Sources ◽  
Stone Formers ◽  
Potential Therapeutic Role

Abstract Objectives Renal fibrosis, a key feature of progressive chronic kidney dysfunction, is characterized by an excessive deposition of extracellular matrix proteins following injury. It is generally the result of sustained glomerular or tubular injury induced by several factors including pro-inflammatory proteins and oxidative stress. We investigated changes in gene expression that could contribute to renal fibrosis in cats with kidney disease or calcium oxalate stone formers (CaOx) at necropsy Methods At the time of death the circulating levels of creatinine, SDMA, as well as blood urea nitrogen, all markers of kidney decline in cats, were significantly higher in cats with renal disease (n = 11) or CaOx (n = 12) when compared to controls (n = 19). Results Using RNAseq in renal cortex tissue, we found a significant decrease in Krüppel-like factor 15 (KLF15), a zinc-finger transcription factor in cats with kidney disease (–1.99 fold, P < 0.001) and CaOx (–1.89, P < 0.001) when compared to controls. Given that KLF15 can attenuate fibrosis by inhibiting the actions of TGF-β, a key regulator of fibrosis, our results indicate that a lower level of KLF15 in kidney disease and CaOx may contribute to renal fibrosis. Consistent with this, there was an increase in all three forms of transforming growth factor-β (TGF-β1, TGF-β2, and TGF-β3), a potent initiator of renal fibrosis, in both groups compared to controls. There was also a significant increase in the expression of BMP-1, a growth factor belonging to the TGF-β superfamily and pro-fibrotic, in cats with kidney disease (2.48 fold) and stone formers (1.72 fold), compared to controls (both P < 0.01). Further, BMP-7, an endogenous inhibitor of TGF-β signaling in fibrosis and whose potential therapeutic role in treating CKD and reversing fibrosis has been documented, was modestly decreased in both groups (both less than 1.5 fold) compared to controls. A decrease was also seen in CRIM 1, a protein associated with podocyte filtration function and whose reduction is associated with fibrosis, in both groups Conclusions Our data show evidence of renal fibrosis markers that could have contributed to a progressive decline in kidney function. In summary, a nutritional therapy to slow the progression of kidney dysfunction may benefit from the inclusion of dietary ingredients that attenuate renal fibrosis in cats. Funding Sources Funded by Hills PNC, Inc.

ASK1/p38 signaling in renal tubular epithelial cells promotes renal fibrosis in the mouse obstructed kidney

2014 ◽  
Vol 307 (11) ◽  
pp. F1263-F1273 ◽  
Author(s):  
Frank Y. Ma ◽  
Greg H. Tesch ◽  
David J. Nikolic-Paterson
Keyword(s):  
Growth Factor ◽  
Epithelial Cells ◽  
Renal Fibrosis ◽  
Transforming Growth Factor ◽  
Smooth Muscle Actin ◽  
Transforming Growth Factor Β ◽  
Tubular Epithelial Cells ◽  
Monocyte Chemoattractant Protein 1 ◽  
Main Site ◽  
Jnk Activation

Stress-activated kinases p38 MAPK and JNK promote renal fibrosis; however, how the pathways by which these kinases are activated in kidney disease remain poorly defined. Apoptosis signal-regulating kinase 1 (ASK1/MAPKKK5) is a member of the MAPKKK family that can induce activation of p38 and JNK. The present study examined whether ASK1 induces p38/JNK activation and renal fibrosis in unilateral ureteric obstruction (UUO) using wild-type (WT) and Ask1-deficient ( Ask1−/−) mice. Basal p38 and JNK activation in WT kidneys was increased three- to fivefold in day 7 UUO mice in association with renal fibrosis. In contrast, there was no increase in p38 activation in Ask1−/− UUO mice, whereas JNK activation was only partially increased. The progressive increase in kidney collagen (hydroxyproline) content seen on days 7 and 12 of UUO in WT mice was significantly reduced in Ask1−/− UUO mice in association with reduced α-smooth muscle actin-positive myofibroblast accumulation. However, cultured WT and Ask1−/− renal fibroblasts showed equivalent proliferation and matrix production, indicating that ASK1 acts indirectly on fibroblasts. Tubular epithelial cells are the main site of p38 activation in the obstructed kidney. Angiotensin II and H2O2, but not IL-1 or lipopolysaccharide, induced p38 activation and upregulation of transforming growth factor-β1, platelet-derived growth factor-B, and monocyte chemoattractant protein-1 production was suppressed in Ask1−/− tubular epithelial cells. In addition, macrophage accumulation was significantly inhibited in Ask1−/− UUO mice. In conclusion, ASK1 is an important upstream activator of p38 and JNK signaling in the obstructed kidney, and ASK1 is a potential therapeutic target in renal fibrosis.

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