Faculty Opinions recommendation of Pharmacological targeting of BET proteins inhibits renal fibroblast activation and alleviates renal fibrosis.

2017 ◽  
Author(s):  
Timothy McKinsey
Keyword(s):  
Renal Fibrosis ◽  
Fibroblast Activation

Apigenin Alleviates Renal Fibroblast Activation through AMPK and ERK Signaling Pathways In Vitro

2020 ◽  
Vol 21 (11) ◽  
pp. 1107-1118
Author(s):  
Ningning Li ◽  
Zhan Wang ◽  
Tao Sun ◽  
Yanfei Lei ◽  
Xianghua Liu ◽  
...  
Keyword(s):  
Renal Fibrosis ◽  
Transforming Growth Factor ◽  
Therapeutic Potential ◽  
Protective Role ◽  
Fibroblast Proliferation ◽  
Fibroblast Activation ◽  
And Function ◽  
Activated Fibroblasts ◽  
Tgf Β1

Objective: Renal fibrosis is a common pathway leading to the progression of chronic kidney disease. Activated fibroblasts contribute remarkably to the development of renal fibrosis. Although apigenin has been demonstrated to play a protective role from fibrotic diseases, its pharmacological effect on renal fibroblast activation remains largely unknown. Materials and Methods: Here, we examined the functional role of apigenin in the activation of renal fibroblasts response to transforming growth factor (TGF)-β1 and its potential mechanisms. Cultured renal fibroblasts (NRK-49F) were exposed to apigenin (1, 5, 10 and 20 μM), followed by the stimulation of TGF-β1 (2 ng/mL) for 24 h. The markers of fibroblast activation were determined. In order to confirm the anti-fibrosis effect of apigenin, the expression of fibrosis-associated genes in renal fibroblasts was assessed. As a consequence, apigenin alleviated fibroblast proliferation and fibroblastmyofibroblast differentiation induced by TGF-β1. Result: Notably, apigenin significantly inhibited the fibrosis-associated genes expression in renal fibroblasts. Moreover, apigenin treatment significantly increased the phosphorylation of AMP-activated protein kinase (AMPK). Apigenin treatment also obviously reduced TGF-β1 induced phosphorylation of ERK1/2 but not Smad2/3, p38 and JNK MAPK in renal fibroblasts. Conclusion: In a summary, these results indicate that apigenin inhibits renal fibroblast proliferation, differentiation and function by AMPK activation and reduced ERK1/2 phosphorylation, suggesting it could be an attractive therapeutic potential for the treatment of renal fibrosis.

scholarly journals Blocking the Class I Histone Deacetylase Ameliorates Renal Fibrosis and Inhibits Renal Fibroblast Activation via Modulating TGF-Beta and EGFR Signaling

PLoS ONE ◽  
2013 ◽  
Vol 8 (1) ◽  
pp. e54001 ◽  
Author(s):  
Na Liu ◽  
Song He ◽  
Li Ma ◽  
Murugavel Ponnusamy ◽  
Jinhua Tang ◽  
...  
Keyword(s):  
Histone Deacetylase ◽  
Renal Fibrosis ◽  
Class I ◽  
Tgf Beta ◽  
Egfr Signaling ◽  
Fibroblast Activation

Tubule‐derived INHBB promotes interstitial fibroblast activation and renal fibrosis

2021 ◽  
Author(s):  
Yanyan Sun ◽  
Huimin Cai ◽  
Jia Ge ◽  
Fang Shao ◽  
Zhen Huang ◽  
...  
Keyword(s):  
Renal Fibrosis ◽  
Fibroblast Activation

scholarly journals Recombinant N–Terminal Slit2 Inhibits TGF-β–Induced Fibroblast Activation and Renal Fibrosis

2016 ◽  
Vol 27 (9) ◽  
pp. 2609-2615 ◽  
Author(s):  
Darren A. Yuen ◽  
Yi-Wei Huang ◽  
Guang-Ying Liu ◽  
Sajedabanu Patel ◽  
Fei Fang ◽  
...  
Keyword(s):  
Renal Fibrosis ◽  
Fibroblast Activation

scholarly journals The IL-4 receptor α has a critical role in bone marrow–derived fibroblast activation and renal fibrosis

2017 ◽  
Vol 92 (6) ◽  
pp. 1433-1443 ◽  
Author(s):  
Hua Liang ◽  
Zhengmao Zhang ◽  
Jingyin Yan ◽  
Yuguo Wang ◽  
Zhaoyong Hu ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Renal Fibrosis ◽  
Critical Role ◽  
Fibroblast Activation

scholarly journals JAK3/STAT6 Stimulates Bone Marrow–Derived Fibroblast Activation in Renal Fibrosis

2015 ◽  
Vol 26 (12) ◽  
pp. 3060-3071 ◽  
Author(s):  
Jingyin Yan ◽  
Zhengmao Zhang ◽  
Jun Yang ◽  
William E. Mitch ◽  
Yanlin Wang
Keyword(s):  
Bone Marrow ◽  
Renal Fibrosis ◽  
Fibroblast Activation

scholarly journals Src inhibition blocks renal interstitial fibroblast activation and ameliorates renal fibrosis

2016 ◽  
Vol 89 (1) ◽  
pp. 68-81 ◽  
Author(s):  
Yanli Yan ◽  
Li Ma ◽  
Xiaoxu Zhou ◽  
Murugavel Ponnusamy ◽  
Jinhua Tang ◽  
...  
Keyword(s):  
Renal Fibrosis ◽  
Fibroblast Activation

scholarly journals Effect of Shenkang on renal fibrosis and activation of renal interstitial fibroblasts through the JAK2/STAT3 pathway

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Tianyu Qin ◽  
You Wu ◽  
Tonghua Liu ◽  
Lili Wu
Keyword(s):  
Renal Fibrosis ◽  
Sham Group ◽  
Smooth Muscle Actin ◽  
Protective Action ◽  
Underlying Mechanism ◽  
Cytokine Signaling ◽  
Stat3 Pathway ◽  
Fibroblast Activation

Abstract Background Activation of renal fibroblasts is a critical mechanism in the process of renal fibrosis. As a commonly used herbal formula, Shenkang (SK) has been found to attenuate renal fibrosis and renal parenchyma destruction. However, the effect of SK on renal fibroblast activation in unilateral ureteral obstruction (UUO) mice and its molecular mechanism remain undetermined. The present study was performed to elucidate the effect of SK on renal fibroblast activation and renal fibrosis, as well as the potential underlying mechanism, in both NRK-49F cells and UUO mice. Methods NRK-49F cells were stimulated with 10 ng/ml TGF-β1 for 48 h. After SK treatment, the CCK-8 method was used to evaluate cell viability. Thirty-six C57BL/6 mice were randomly divided into the sham group, UUO group, angiotensin receptor blocker (ARB) group, and SK high-, moderate- and low-dose groups. UUO was induced in mice except those in the sham group. Drugs were administered 1 day later. On the 13th day, the fractional anisotropy (FA) value was determined by MRI to evaluate the degree of renal fibrosis. After 14 days, serum indexes were assessed. Hematoxylin and eosin (HE) and Sirius red staining were used to observe pathological morphology and the degree of fibrosis of the affected kidney. Western blotting and PCR were used to assess the expression of related molecules in both cells and animals at the protein and gene levels. Results Our results showed that SK reduced extracellular matrix (ECM) and α-smooth muscle actin (α-SMA) expression both in vitro and in vivo and attenuated renal fibrosis and the pathological lesion degree after UUO, suppressing JAK2/STAT3 activation. Furthermore, we found that SK regulated the JAK2/STAT3 pathway regulators peroxiredoxin 5 (Prdx5) in vitro and suppressor of cytokine signaling protein 1 (SOCS1) and SOCS3 in vivo. Conclusions These results indicated that SK inhibited fibroblast activation by regulating the JAK2/STAT3 pathway, which may be a mechanism underlying its protective action in renal fibrosis.

scholarly journals STAT6 Deficiency Attenuates Myeloid Fibroblast Activation and Macrophage Polarization in Experimental Folic Acid Nephropathy

Cells ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 3057
Author(s):  
Baihai Jiao ◽  
Changlong An ◽  
Hao Du ◽  
Melanie Tran ◽  
Penghua Wang ◽  
...  
Keyword(s):  
Folic Acid ◽  
Kidney Disease ◽  
Knockout Mice ◽  
Renal Fibrosis ◽  
Matrix Protein ◽  
Macrophage Polarization ◽  
Extracellular Matrix Protein ◽  
M2 Macrophage ◽  
Fibroblast Activation ◽  
M2 Macrophage Polarization

Renal fibrosis is a pathologic feature of chronic kidney disease, which can lead to end-stage kidney disease. Myeloid fibroblasts play a central role in the pathogenesis of renal fibrosis. However, the molecular mechanisms pertaining to myeloid fibroblast activation remain to be elucidated. In the present study, we examine the role of signal transducer and activator of transcription 6 (STAT6) in myeloid fibroblast activation, macrophage polarization, and renal fibrosis development in a mouse model of folic acid nephropathy. STAT6 is activated in the kidney with folic acid nephropathy. Compared with folic-acid-treated wild-type mice, STAT6 knockout mice had markedly reduced myeloid fibroblasts and myofibroblasts in the kidney with folic acid nephropathy. Furthermore, STAT6 knockout mice exhibited significantly less CD206 and PDGFR-β dual-positive fibroblast accumulation and M2 macrophage polarization in the kidney with folic acid nephropathy. Consistent with these findings, STAT6 knockout mice produced less extracellular matrix protein, exhibited less severe interstitial fibrosis, and preserved kidney function in folic acid nephropathy. Taken together, these results have shown that STAT6 plays a critical role in myeloid fibroblasts activation, M2 macrophage polarization, extracellular matrix protein production, and renal fibrosis development in folic acid nephropathy. Therefore, targeting STAT6 may provide a novel therapeutic strategy for fibrotic kidney disease.

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