Augmenter of liver regeneration ameliorates renal fibrosis in rats with obstructive nephropathy

Chen, Guo-tao; Zhang, Ling; Liao, Xiaohui; Yan, Ruyu; Li, Ying; Sun, Hang; Guo, Hui; Liu, Qi

doi:10.1042/bsr20140038

Cited by 8 publications

(3 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

Section: Endogenous Antifibrotic Factorsmentioning

confidence: 99%

“…The growth factor augmenter of liver regeneration (ALR) has actions similar to those of HGF (Chen et al, 2014). Chen and colleagues reported that endogenous ALR attenuates renal fibrosis in the UUO rat model (Chen et al, 2014). In vitro experiments showed that recombinant human ALR inhibits EMT by inhibiting TGFβR2 expression and TGF-β1-induced signaling (Liao et al, 2014).…”

Section: Endogenous Antifibrotic Factorsmentioning

confidence: 99%

See 1 more Smart Citation

Inflammation and renal fibrosis: Recent developments on key signaling molecules as potential therapeutic targets

Booz

Wang

et al. 2018

European Journal of Pharmacology

255

200

View full text Add to dashboard Cite

Chronic kidney disease (CKD) is a major public health issue. At the histological level, renal fibrosis is the final common pathway of progressive kidney disease irrespective of the initial injury. Considerable evidence now indicates that renal inflammation plays a central role in the initiation and progression of CKD. Some of the inflammatory signaling molecules involved in CKD include: monocyte chemoattractant protein-1 (MCP-1), bradykinin B receptor (BR), nuclear factor κB (NF-κB), tumor necrosis factor-α (TNFα), transforming growth factor β (TGF-β), and platelet-derived growth factor (PDGF). Multiple antifibrotic factors, such as interleukin-10 (IL-10), interferon-γ (IFN-γ), bone morphogenetic protein-7 (BMP-7), hepatocyte growth factor (HGF) are also downregulated in CKD. Therefore, restoration of the proper balance between pro- and antifibrotic signaling pathways could serve as a guiding principle for the design of new antifibrotic strategies that simultaneously target many pathways. The purpose of this review is to summarize the existing body of knowledge regarding activation of cytokine pathways and infiltration of inflammatory cells as a starting point for developing novel antifibrotic therapies to prevent progression of CKD.

show abstract

Section: Endogenous Antifibrotic Factorsmentioning

confidence: 99%

Section: Endogenous Antifibrotic Factorsmentioning

confidence: 99%

Inflammation and renal fibrosis: Recent developments on key signaling molecules as potential therapeutic targets

Booz

Wang

et al. 2018

European Journal of Pharmacology

255

200

View full text Add to dashboard Cite

show abstract

“…Moreover, ALR is highly expressed in I/R kidneys as a hepatocyte growth factor [13,14]. Our previous work has indicated that exogenous ALR can protect kidney tissues from I/R injury through inhibiting apoptosis of renal TEC [15][16][17]. Recent researches have revealed that ALR can also modulate T helper 1 (Th1) cell cytokines and immune cells [18][19][20].…”

Section: Introductionmentioning

confidence: 99%

Augmenter of Liver Regeneration (ALR) Protects Kidney from Ischemia/Reperfusion (I/R) Injury via Regulation of TLR4/MAPK Signaling Pathway

Liu

Xiong

et al. 2022

Journal of Immunology Research

Self Cite

View full text Add to dashboard Cite

Toll-like receptor 4 (TLR4) can mediate innate activation and inflammation, and it is typically expressed within the ischemic kidney. Augmenter of liver regeneration (ALR) acts as an immunoregulator with a high expression in the kidney induced by renal ischemia/reperfusion (I/R) injury. Exogenous ALR has indicated a role in protecting the kidney from I/R injury. The protective effect of ALR is due to the immune regulatory function which remains to be elucidated. In this study, rats induced by renal I/R were treated with recombinant human ALR (rhALR) and demonstrated that the animals were protected from kidney I/R injury, implying that the rhALR-treated rats had less tubular damage than those untreated rats. Meanwhile, tubular epithelial cell apoptosis, neutrophil (24 h) and macrophage (72 h) infiltration to tubulointerstitium, and levels of inflammatory cytokines were decreased considerably in the rhALR-treated rats as compared to control. Additionally, rhALR could downregulate mRNA expression of TLR4 endogenous ligands and restrain its activation in renal I/R injury rats. It has also been proved that anti-rhALR antibody blocked the inhibition of rhALR of the immune inflammatory response in hypoxia/reoxygenation (H/R) injury in vitro. In rhALR+anti-rhALR antibody-intervened H/R cells, the expression of inflammatory cytokines was upregulated compared with the rhALR-treated cells. Taken together, rhALR could regulate the TLR4 signaling pathway to relieve inflammatory response, thereby protecting renal I/R injury, indicating that ALR is likely to be introduced to develop novel immune therapies for renal I/R injury.

show abstract

Role of the ER stress in prostaglandin E2/E-prostanoid 2 receptor involved TGF-β1-induced mice mesangial cell injury

Wang

Pan

et al. 2015

Mol Cell Biochem

View full text Add to dashboard Cite

This study aims to investigate the relationship between prostaglandin E2 E-prostanoid 2 receptor (EP2) and Endoplasmic reticulum (ER) stress in transforming growth factor-β1 (TGF-β1)-induced mouse glomerular mesangial cells (MCs) injury. We cultured primary WT, EP2(-/-) MCs (EP2 deleted), and adenovirus-EP2-infected WT MCs (EP2 overexpressed). PCR, Western blot, flow cytometry, and immunohistochemical technique were used in in vitro and in vivo experiments. We found that TGF-β1-induced PGE2 synthesis decreased in EP2-deleted MCs and increased in EP2-overexpressed MCs. EP2 deficiency in these MCs augmented the coupling of TGF-β1 to ER stress-associated proteins [chaperone glucose-regulated protein 78 (GRP78), transient receptor potential channel 1 (TRPC1), and transient receptor potential channel 4 (TRPC4)], and upregulation of EP2 showed no significant change of GRP78, but augmented the expression of TRPC1, while TRPC4 expression was downregulated in comparison to normal MCs. In addition, EP2 deficiency in MCs augmented TGF-β1-induced fibronectin (FN), cyclooxygenase-2 (COX2), and CyclinD1 expression. Silencing of EP2 also strengthened TGF-β1-induced extracellular-signal-regulated kinase 1/2 (ERK1/2) phosphorylation. Flow Cytometry showed that silencing of EP2 significantly promoted the apoptosis of MCs. In contrast, EP2 overexpression reversed the effects of EP2 deficiency. 8 weeks after 5/6 nephrectomy (Nx), blood urea nitrogen and creatinine concentrations were significantly increased in EP2(-/-) 5/6Nx mice as compared to those of WT 5/6Nx mice. The pathological changes in kidney of EP2(-/-) mice were markedly aggravated compared with WT mice. Immunohistochemical analysis showed significant augment of TRPC4 and ORP150 in the kidney of EP2(-/-) mice compared with WT mice. Considering all the findings, it is suggested that increased expression of EP2 may prevent TGF-β1-induced MCs damage through ER stress regulatory pathway.

show abstract

Augmenter of liver regeneration ameliorates renal fibrosis in rats with obstructive nephropathy

Cited by 8 publications

References 39 publications

Inflammation and renal fibrosis: Recent developments on key signaling molecules as potential therapeutic targets

Inflammation and renal fibrosis: Recent developments on key signaling molecules as potential therapeutic targets

Augmenter of Liver Regeneration (ALR) Protects Kidney from Ischemia/Reperfusion (I/R) Injury via Regulation of TLR4/MAPK Signaling Pathway

Role of the ER stress in prostaglandin E2/E-prostanoid 2 receptor involved TGF-β1-induced mice mesangial cell injury

Contact Info

Product

Resources

About