Novel Targets for Therapy of Renal Fibrosis

Prakoura, Niki; Hadchouel, Juliette; Chatziantoniou, Christos

doi:10.1369/0022155419849386

Cited by 26 publications

(24 citation statements)

References 115 publications

(174 reference statements)

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“…As described by others, Cx43 might probably be related to the endothelium of lymphatic vessels [ 44 , 49 ]. Since multiple studies suggest a link between Cx43 expression and (pro-)fibrotic conditions of the kidney [ 17 , 19 , 50 ], even consider Cx43 to be a therapeutic target for therapy of renal fibrosis [ 17 , 51 ], further investigation concerning exact localization and function of Cx43 in renal interstitium is needed.…”

Section: Discussionmentioning

confidence: 99%

Connexin mRNA distribution in adult mouse kidneys

Geis

Boudriot

Wagner

2021

Pflugers Arch - Eur J Physiol

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Kidneys are thought to express eight different connexin isoforms (i.e., Cx 26, 30, 32, 37, 40, 43, 45, and 46), which form either hemichannels or gap junctions serving to intercellular communication and functional synchronization. Proper function of connexins has already been shown to be crucial for regulation of renal hemodynamics and renin secretion, and there is also growing evidence for connexins to play a role in pathologic conditions such as renal fibrosis or diabetic nephropathy. Therefore, exact intrarenal localization of the different connexin isoforms gains particular interest. Until now intrarenal expression of connexins has mainly been examined by immunohistochemistry, which in part generated conflicting results depending on antibodies and fixation protocols used. In this work, we used fluorescent RNAscope as an alternative technical approach to localize renal connexin mRNAs in healthy mouse kidneys. Addition of RNAscope probes for cell type specific mRNAs was used to assign connexin mRNA signals to specific cell types. We hereby found Cx26 mRNA strongly expressed in proximal tubules, Cx30 mRNA was selectively detected in the urothelium, and Cx32 mRNA was found in proximal tubules and to a lesser extent also in collecting ducts. Cx37 mRNA was mainly associated with vascular endothelium, Cx40 mRNA was largely found in glomerular mesangial and less in vascular endothelial cells, Cx43 mRNA was sparsely expressed by interstitial cells of all kidney zones, and Cx45 mRNA was predominantly found in smooth muscle cell layers of both blood vessels and ureter as well as in mesangial and interstitial (fibroblastic) cells. Cx46 mRNA could not be detected. In summary our results essentially confirm previous data on connexin expression in the renal vasculature and in glomeruli. In addition, they demonstrate strong connexin gene expression in proximal tubules, and they suggest significant connexin expression in resident tubulointerstitial cells.

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Section: Discussionmentioning

confidence: 99%

Connexin mRNA distribution in adult mouse kidneys

Geis

Boudriot

Wagner

2021

Pflugers Arch - Eur J Physiol

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“…The characteristic typical signs of renal fibrosis are the development of cellular and tissue proinflammatory stress in the kidneys, including oxidative stress, the formation of inflammasomes, and factors of the proinflammatory secretory phenotype [ 98 , 99 ]. Thus, regardless of the precise causal mechanism or localization of the process, the universal effect of cytokines and other mediators of various renal cells on the development of renal fibrosis has been demonstrated in people and animals [ 100 , 101 , 102 , 103 , 104 , 105 ], as listed below. angiotensin II (Ang-II), ET-1, adenosine (ADO), ROS; transforming growth factor-β (TGF-β); growth factors of platelets (PDGF), connective tissue (CTGF), and fibroblasts-23 (FGF-23); chemokines: monocyte chemoattractant protein-1 (MCP-1, CCL2) and stromal cell factor-1 (SDF-1, CXCL12); cytokines: TNF-α, IL-6, IL-11, IL-18, and IL-20; kidney damage molecule-1 (KIM-1); direct intercellular contact interactions of Notch family receptors and Notch ligands involved in the epithelial–mesenchymal transition.…”

Section: Typical Low-intensity Inflammatory Processes In Ckd and Esrdmentioning

confidence: 99%

The Pathogenesis of End-Stage Renal Disease from the Standpoint of the Theory of General Pathological Processes of Inflammation

Гусев

Соломатина

Zhuravleva

et al. 2021

IJMS

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Chronic kidney disease can progress to end-stage chronic renal disease (ESRD), which requires the use of replacement therapy (dialysis or kidney transplant) in life-threatening conditions. In ESRD, irreversible changes in the kidneys are associated with systemic changes of proinflammatory nature and dysfunctions of internal organs, skeletal muscles, and integumentary tissues. The common components of ESRD pathogenesis, regardless of the initial nosology, are (1) local (in the kidneys) and systemic chronic low-grade inflammation (ChLGI) as a risk factor for diabetic kidney disease and its progression to ESRD, (2) inflammation of the classical type characteristic of primary and secondary autoimmune glomerulonephritis and infectious recurrent pyelonephritis, as well as immune reactions in kidney allograft rejection, and (3) chronic systemic inflammation (ChSI), pathogenetically characterized by latent microcirculatory disorders and manifestations of paracoagulation. The development of ChSI is closely associated with programmed hemodialysis in ESRD, as well as with the systemic autoimmune process. Consideration of ESRD pathogenesis from the standpoint of the theory of general pathological processes opens up the scope not only for particular but also for universal approaches to conducting pathogenetic therapies and diagnosing and predicting systemic complications in severe nephropathies.

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“…Interestingly, inflammatory responses are central to the progression of renal fibrosis (Zhao et al, 2015;Chen et al, 2019). They involve various cytokine-mediated multi-signaling pathways, including transforming growth factor-beta (TGF-β), tumor necrosis factor-alpha (TNF-α), and leukocyte mediators (Lv et al, 2018;Chen et al, 2018a;Prakoura et al, 2019). Interleukin 33 (IL-33), the gene for which is located on chromosome 9, is a newly discovered member of the IL-1 cytokine family and a pivotal regulator of inflammatory and immune responses (Molofsky et al, 2015;Di Salvo et al, 2018;Chen et al, 2020).…”

Section: Introductionmentioning

confidence: 99%

Interleukin-33/ Suppression of Tumorigenicity 2 in Renal Fibrosis: Emerging Roles in Prognosis and Treatment

Tan

Jing

2022

Front. Physiol.

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Chronic kidney disease (CKD) is a major public health problem that affects more than 10% of the population worldwide and has a high mortality rate. Therefore, it is necessary to identify novel treatment strategies for CKD. Incidentally, renal fibrosis plays a central role in the progression of CKD to end-stage renal disease (ESRD). The activation of inflammatory pathways leads to the development of renal fibrosis. In fact, interleukin-33 (IL-33), a newly discovered member of the interleukin 1 (IL-1) cytokine family, is a crucial regulator of the inflammatory process. It exerts pro-inflammatory and pro-fibrotic effects via the suppression of tumorigenicity 2 (ST2) receptor, which, in turn, activates other inflammatory pathways. Although the role of this pathway in cardiac, pulmonary, and hepatic fibrotic diseases has been extensively studied, its precise role in renal fibrosis has not yet been completely elucidated. Recent studies have shown that a sustained activation of IL-33/ST2 pathway promotes the development of renal fibrosis. However, with prolonged research in this field, it is expected that the IL-33/ST2 pathway will be used as a diagnostic and prognostic tool for renal diseases. In addition, the IL-33/ST2 pathway seems to be a new target for the future treatment of CKD. Here, we review the mechanisms and potential applications of the IL-33/ST2 pathway in renal fibrosis; such that it can help clinicians and researchers to explore effective treatment options and develop novel medicines for CKD patients.

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Novel Targets for Therapy of Renal Fibrosis

Cited by 26 publications

References 115 publications

Connexin mRNA distribution in adult mouse kidneys

Connexin mRNA distribution in adult mouse kidneys

The Pathogenesis of End-Stage Renal Disease from the Standpoint of the Theory of General Pathological Processes of Inflammation

Interleukin-33/ Suppression of Tumorigenicity 2 in Renal Fibrosis: Emerging Roles in Prognosis and Treatment

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