Transforming Growth Factor-β and Long Non-coding RNA in Renal Inflammation and Fibrosis

Gu, Yue-Yu; Dou, Jing-Yun; Huang, Xiao‐Ru; Liu, Xusheng; Lan, Hui‐Yao

doi:10.3389/fphys.2021.684236

Cited by 19 publications

(13 citation statements)

References 172 publications

(176 reference statements)

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“…However, this reaction will become a pathogenic factor when kidney damage is prolonged and overreacted, eventually giving rise of end-stage kidney disease. Likewise, continuous renal inflammation, including secretion of pro-fibrotic factors, chemokines and cytokines, which could prompt the fibrosis ( 113 ). Renal fibrosis is a complicated disorder characterized by the destruction of kidney parenchyma, composed by the abnormal accumulation of ECM and lower glomerular filtration rate ( 114 ).…”

Section: Grk2 and Fibrotic Diseasementioning

confidence: 99%

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G Protein-Coupled Receptor Kinase 2 as Novel Therapeutic Target in Fibrotic Diseases

Shan

et al. 2022

Front. Immunol.

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G protein-coupled receptor kinase 2 (GRK2), an important subtype of GRKs, specifically phosphorylates agonist-activated G protein-coupled receptors (GPCRs). Besides, current research confirms that it participates in multiple regulation of diverse cells via a non-phosphorylated pathway, including interacting with various non-receptor substrates and binding partners. Fibrosis is a common pathophysiological phenomenon in the repair process of many tissues due to various pathogenic factors such as inflammation, injury, drugs, etc. The characteristics of fibrosis are the activation of fibroblasts leading to myofibroblast proliferation and differentiation, subsequent aggerate excessive deposition of extracellular matrix (ECM). Then, a positive feedback loop is occurred between tissue stiffness caused by ECM and fibroblasts, ultimately resulting in distortion of organ architecture and function. At present, GRK2, which has been described as a multifunctional protein, regulates copious signaling pathways under pathophysiological conditions correlated with fibrotic diseases. Along with GRK2-mediated regulation, there are diverse effects on the growth and apoptosis of different cells, inflammatory response and deposition of ECM, which are essential in organ fibrosis progression. This review is to highlight the relationship between GRK2 and fibrotic diseases based on recent research. It is becoming more convincing that GRK2 could be considered as a potential therapeutic target in many fibrotic diseases.

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Section: Grk2 and Fibrotic Diseasementioning

confidence: 99%

“…inflammation, including secretion of pro-fibrotic factors, chemokines and cytokines, which could prompt the fibrosis (113). Renal fibrosis is a complicated disorder characterized by the destruction of kidney parenchyma, composed by the abnormal accumulation of ECM and lower glomerular filtration rate (114).…”

Section: Renal Fibrosismentioning

confidence: 99%

G Protein-Coupled Receptor Kinase 2 as Novel Therapeutic Target in Fibrotic Diseases

Shan

et al. 2022

Front. Immunol.

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“…Acute kidney dysfunction impairs the essential physiological homeostasis of the body. Although the kidneys have the remarkable ability to regenerate, progressive inflammation may eventually trigger renal fibrosis and lead to CKD ( Gu et al, 2021 ). Salvia miltiorrhiza and its active compounds have been reported to have anti-inflammatory effects in the kidney disease ( Gao et al, 2018 ).…”

Section: Discussionmentioning

confidence: 99%

“…The initial renal insults may induce the infiltration of inflammatory leukocytes within the glomerulus and tubulointerstitial area. Unresolved renal inflammation can impair the function of the nephrons and lead to a reduction in the estimated glomerular filtration rate (eGFR) ( Gu et al, 2021 ). We are now clear that renal inflammation is the central pathogenic mechanism that drives AKI.…”

Section: Introductionmentioning

confidence: 99%

Salvia miltiorrhiza Bunge (Danshen) and Bioactive Compound Tanshinone IIA Alleviates Cisplatin-Induced Acute Kidney Injury Through Regulating PXR/NF-κB Signaling

et al. 2022

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Objective: The present study aims to provide evidence on the potential protective role of Salvia miltiorrhiza Bunge (Danshen) and its bioactive compound Tanshinone IIA (TanIIA) in AKI and to reveal the specific regulatory function of PXR/NF-κB signaling in AKI-induced renal inflammation.Methods: A network pharmacological analysis was used to study target genes and regulatory networks in the treatment of Salvia miltiorrhiza on AKI. Further experiments with in vivo AKI mouse model and in vitro studies were applied to investigate the renal protective effect of TanIIA in AKI. The mechanisms of TanIIA regulating PXR/NF-κB signaling in renal inflammation were also studied.Results: Network pharmacology had suggested the nuclear receptor family as new therapeutic targets of Salvia miltiorrhiza in AKI treatment. The in vivo studies had demonstrated that TanIIA improved renal function and inflammation by reducing necrosis and promoting the proliferation of tubular epithelial cells. Improved renal arterial perfusion in AKI mice with TanIIA treatment was also recorded by ultrasonography. In vitro studies had shown that TanIIA ameliorated renal inflammation by activating the PXR while inhibiting PXR-mediated NF-κB signaling. The results had suggested a role of PXR activation against AKI-induced renal inflammation.Conclusion:Salvia miltiorrhiza Bunge (Danshen) may protect the kidneys against AKI by regulating nuclear receptors. TanIIA improved cell necrosis proliferation and reduced renal inflammation by upregulating the expression of the PXR and inhibiting NF-κB signaling in a PXR-dependent manner. The PXR may be a potential therapeutic target for AKI treatment.

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“…Increasing evidence shows that renal inflammation and fibrosis are also tightly regulated by a few Smad3-dependent long noncoding RNAs (lncRNAs) 98 (Figure 4 ). Indeed, research into the lncRNAs is more promising for a better understanding of the pathogenic mechanisms of kidney diseases.…”

Section: Regulation Of Smad3-dependent Micrornas and Lncrna In Renal ...mentioning

confidence: 99%

Smad3 Signatures in Renal Inflammation and Fibrosis

Wu¹,

Wang²,

Yu³

et al. 2022

Int. J. Biol. Sci.

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Renal inflammation and fibrosis are key pathological features of acute kidney injury (AKI) and chronic kidney disease (CKD). Smad3 is a critical mediator of TGF-β signaling and plays a pathogenic role in both renal inflammation and fibrosis. Smad3 can be activated not only by TGF-β1 but also by many stress molecules including angiotensin II (Ang II), advanced end products (AGEs), and C-reactive protein (CRP) under disease conditions. In addition, Smad3 can interact with other signaling pathways, such as the ERK/p38 MAPK and NF-κB pathways, to mediate renal inflammation and fibrosis. Mechanistically, Smad3 transcriptionally regulates many downstream target genes including microRNAs and long non-coding RNAs to cause cell death, inflammation, and fibrosis. Thus, targeting Smad3 or its downstream genes specifically related to renal inflammation and fibrosis should provide a novel therapeutic strategy to combat kidney diseases.

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Transforming Growth Factor-β and Long Non-coding RNA in Renal Inflammation and Fibrosis

Cited by 19 publications

References 172 publications

G Protein-Coupled Receptor Kinase 2 as Novel Therapeutic Target in Fibrotic Diseases

G Protein-Coupled Receptor Kinase 2 as Novel Therapeutic Target in Fibrotic Diseases

Salvia miltiorrhiza Bunge (Danshen) and Bioactive Compound Tanshinone IIA Alleviates Cisplatin-Induced Acute Kidney Injury Through Regulating PXR/NF-κB Signaling

Smad3 Signatures in Renal Inflammation and Fibrosis

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