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Review
. 2018 Feb 5:820:65-76.
doi: 10.1016/j.ejphar.2017.12.016. Epub 2017 Dec 8.

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

Wenshan Lv  1 , George W Booz  2 , Yangang Wang  3 , Fan Fan  2 , Richard J Roman  4
Affiliations
Review

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

Wenshan Lv et al. Eur J Pharmacol. .

Abstract

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 B1 receptor (B1R), 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.

Keywords: Antifibrotic therapy; Chronic kidney disease; Cytokines; Inflammation; Renal fibrosis.

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Figures

Fig. 1
Fig. 1. Summary of pro- and anti-fibrotic factors involved in renal inflammation
Renal inflammation plays a central role in the initiation and progression of chronic kidney disease (CKD) by causing fibrosis. Multiple inflammatory signaling molecules are activated that are potential targets for drug development. Multiple antifibrotic factors are also downregulated, thus contributing to the development of CKD indirectly. Therapies aimed at restoring levels of these factors or activating their signaling pathways are an alternative strategy for attenuating renal fibrosis. Restoration of the balance between pro- and antifibrotic signaling pathways could serve as a guiding principle for the design of new antifibrotic strategies to treat CKD.
Fig. 2
Fig. 2. The common pathway in renal fibrosis
In response to renal injury, resident renal cells and infiltrating immune cells produce a number of factors that initiate the processes of renal fibrosis, including TGF-β and ROS. These factors act in concert with various reinforcing factors, such as the sustained activation of receptor tyrosine kinases (RTKs), to activate signal transduction intermediates that drive ECM accumulation and renal fibrosis by multiple means, involving: the formation of fibroblasts with a synthetic phenotype (myofibroblasts) from resident fibroblasts or via the processes of epithelial-to-mesenchymal transition (EMT) or endothelial-to-mesenchymal transition (EndMT), cell death, and the production of pro-inflammatory or profibrotic cytokines (including TGF-β) that feedback to perpetuate the inflammatory and fibrotic cycle. Recent studies have defined a number of endogenous molecules that dampen the fibrotic process by targeting either the reinforcing factors or signaling intermediates. See text for additional details.
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References

    1. Ai J, Nie J, He J, Guo Q, Li M, Lei Y, Liu Y, Zhou Z, Zhu F, Liang M, Cheng Y, Hou FF. GQ5 Hinders Renal Fibrosis in Obstructive Nephropathy by Selectively Inhibiting TGF-beta-Induced Smad3 Phosphorylation. J Am Soc Nephrol. 2015;26:1827–1838. - PMC - PubMed
    1. Akcay A, Nguyen Q, He Z, Turkmen K, Won Lee D, Hernando AA, Altmann C, Toker A, Pacic A, Ljubanovic DG, Jani A, Faubel S, Edelstein CL. IL-33 exacerbates acute kidney injury. J Am Soc Nephrol. 2011;22:2057–2067. - PMC - PubMed
    1. Anders HJ, Belemezova E, Eis V, Segerer S, Vielhauer V, Perez de Lema G, Kretzler M, Cohen CD, Frink M, Horuk R, Hudkins KL, Alpers CE, Mampaso F, Schlondorff D. Late onset of treatment with a chemokine receptor CCR1 antagonist prevents progression of lupus nephritis in MRL-Fas(lpr) mice. J Am Soc Nephrol. 2004;15:1504–1513. - PubMed
    1. Anders HJ, Vielhauer V, Frink M, Linde Y, Cohen CD, Blattner SM, Kretzler M, Strutz F, Mack M, Grone HJ, Onuffer J, Horuk R, Nelson PJ, Schlondorff D. A chemokine receptor CCR-1 antagonist reduces renal fibrosis after unilateral ureter ligation. J Clin Invest. 2002;109:251–259. - PMC - PubMed
    1. Bernhardt A, Fehr A, Brandt S, Jerchel S, Ballhause TM, Philipsen L, Stolze S, Geffers R, Weng H, Fischer KD, Isermann B, Brunner-Weinzierl MC, Batra A, Siegmund B, Zhu C, Lindquist JA, Mertens PR. Inflammatory cell infiltration and resolution of kidney inflammation is orchestrated by the cold-shock protein Y-box binding protein-1. Kidney Int 2017 - PubMed