Less contribution of mast cells to the progression of renal fibrosis in Rat kidneys with chronic renal failure

Baba, Asuka; Tachi, Masahiro; Ejima, Yutaka; Endo, Yasuhiro; Toyama, Hiroaki; Saito, Kazutomo; Abe, Noritaka; Yamauchi, M.; Miura, Chieko; Kazama, Itsuro

doi:10.1111/nep.12733

Cited by 6 publications

(5 citation statements)

References 42 publications

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“…These experiments revealed that MCs did not crucially impact the later phase of the disease and fibrosis development, as no differences became apparent between PBS-and DT-treated animals. Of note in this context, Baba et al (55) recently showed in a rat model of chronic renal failure unchanged fibrosis progression after tranilast treatment, a potent MC stabilizer. Thus, our data strongly support that the degree of initial injury by MCs represents the major factor of pathologic development, calling for early MC-targeting therapeutic interventions as suggested recently (41).…”

Section: Discussionmentioning

confidence: 96%

Early Phase Mast Cell Activation Determines the Chronic Outcome of Renal Ischemia–Reperfusion Injury

Danelli

Madjène

Madera-Salcedo

et al. 2017

The Journal of Immunology

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Ischemia–reperfusion injury (IRI) is an important cause of acute kidney injury that can lead to end-stage renal failure. Although the ensuing inflammatory response can restore homeostasis, a consecutive maladaptive repair and persistent inflammation represent important risk factors for postischemic chronic kidney disease development. In this study, we investigated the role of mast cells in both the early and late phases of the inflammatory response in experimental models of acute and chronic renal IRI using our recently developed mouse model that allows conditional ablation of mast cells. Depletion of mast cells prior to IRI resulted in improved renal function due to diminished local inflammatory cytokine/chemokine levels and neutrophil recruitment to the kidneys after the acute injury phase (48 h post-IRI). Furthermore, although not completely protected, mast cell–depleted mice displayed less organ atrophy and fibrosis than did wild-type mice during the chronic phases (2 and 6 wk post-IRI) of disease development. Conversely, mast cell ablation after the acute phase of IRI had no impact on organ atrophy, tubular necrosis, or fibrosis. Thus, our results suggest a deleterious role of mast cells during the acute inflammatory phase of IRI promoting subsequent fibrosis development, but not during the chronic phase of the disease.

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Section: Discussionmentioning

confidence: 96%

Early Phase Mast Cell Activation Determines the Chronic Outcome of Renal Ischemia–Reperfusion Injury

Danelli

Madjène

Madera-Salcedo

et al. 2017

The Journal of Immunology

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“…In addition, Tranilast was shown to be without effect against fibrosis in rats with chronic renal failure. 244 In a study by Palaniyandi Selvaraj et al 197 , it was demonstrated that disodium cromoglycate reduced the fibrosis during autoimmune myocarditis, and this compound also reduced atrial fibrosis occurring after pressure overload in a mouse model, 199 fibrosis after implantation of biomaterials, 194 kidney fibrosis in the unilateral ureteral obstruction model 188,191 and the development of liver fibrosis in multidrug resistance two knockout mice. 245 However, since cromoglycate has been shown to have effects outside of its impact on MCs, 246 it is not certain that effects of this compound are mediated through MCs as opposed to other targets.…”

Section: Other Pharmacological Approaches To Target Mast Cells In Fmentioning

confidence: 99%

“…However, Tranilast was equally efficient in MC‐competent vs ‐deficient mice, suggesting that the impact of Tranilast was not due to effects mediated by MCs. In addition, Tranilast was shown to be without effect against fibrosis in rats with chronic renal failure . In a study by Palaniyandi Selvaraj et al, it was demonstrated that disodium cromoglycate reduced the fibrosis during autoimmune myocarditis, and this compound also reduced atrial fibrosis occurring after pressure overload in a mouse model, fibrosis after implantation of biomaterials, kidney fibrosis in the unilateral ureteral obstruction model and the development of liver fibrosis in multidrug resistance two knockout mice .…”

Section: Targeting Mast Cell Function In Fibrosismentioning

confidence: 99%

The controversial role of mast cells in fibrosis

Bradding

Pejler

2018

Immunological Reviews

111

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Fibrosis is a medical condition characterized by an excessive deposition of extracellular matrix compounds such as collagen in tissues. Fibrotic lesions are present in many diseases and can affect all organs. The excessive extracellular matrix accumulation in these conditions can often have serious consequences and in many cases be life-threatening. A typical event seen in many fibrotic conditions is a profound accumulation of mast cells (MCs), suggesting that these cells can contribute to the pathology. Indeed, there is now substantialv evidence pointing to an important role of MCs in fibrotic disease. However, investigations from various clinical settings and different animal models have arrived at partly contradictory conclusions as to how MCs affect fibrosis, with many studies suggesting a detrimental role of MCs whereas others suggest that MCs can be protective. Here, we review the current knowledge of how MCs can affect fibrosis.

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“…Renal cross sections were fixed in 4% paraformaldehyde, embedded in paraffin, and deparaffinized in xylene, and then 3 μ m sections were stained with hematoxylin-eosin (H&E) and Masson's trichrome. For fibrosis analysis, Masson's trichrome deposition, expressed as percentages of Masson's trichrome-positive areas relative to the total area, was quantified in each field and averaged, as described in our previous studies [16, 21–23].…”

Section: Methodsmentioning

confidence: 99%

“…Mast cells were identified by their characteristic metachromasia. For quantitative analysis, the numbers of CD3-, ED-1-, toluidine blue-, MPO-, Ki-67-, and α -SMA-positive cells were counted in high-power fields of the cortical interstitium as described in our previous studies [16, 21–23].…”

Section: Methodsmentioning

confidence: 99%

Delayed Rectifier K⁺-Channel Is a Novel Therapeutic Target for Interstitial Renal Fibrosis in Rats with Unilateral Ureteral Obstruction

Abe

Toyama

Saito

et al. 2019

BioMed Research International

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Background Delayed rectifier K+-channel, Kv1.3, is most predominantly expressed in T-lymphocytes and macrophages. In such leukocytes, Kv1.3-channels play pivotal roles in the activation and proliferation of cells, promoting cellular immunity. Since leukocyte-derived cytokines stimulate fibroblasts to produce collagen fibers in inflamed kidneys, Kv1.3-channels expressed in leukocytes would contribute to the progression of tubulointerstitial renal fibrosis. Methods Male Sprague-Dawley rats that underwent unilateral ureteral obstruction (UUO) were used at 1, 2, or 3 weeks after the operation. We examined the histological features of the kidneys and the leukocyte expression of Kv1.3-channels. We also examined the therapeutic effects of a selective channel inhibitor, margatoxin, on the progression of renal fibrosis and the proliferation of leukocytes within the cortical interstitium. Results In rat kidneys with UUO, progression of renal fibrosis and the infiltration of leukocytes became most prominent at 3 weeks after the operation, when Kv1.3-channels were overexpressed in proliferating leukocytes. In the cortical interstitium of margatoxin-treated UUO rat kidneys, immunohistochemistry revealed reduced expression of fibrosis markers. Additionally, margatoxin significantly decreased the numbers of leukocytes and suppressed their proliferation. Conclusions This study clearly demonstrated that the numbers of T-lymphocytes and macrophages were markedly increased in UUO rat kidneys with longer postobstructive days. The overexpression of Kv1.3-channels in leukocytes was thought to be responsible for the proliferation of these cells and the progression of renal fibrosis. This study strongly suggested the therapeutic usefulness of targeting lymphocyte Kv1.3-channels in the treatment of renal fibrosis.

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Less contribution of mast cells to the progression of renal fibrosis in Rat kidneys with chronic renal failure

Cited by 6 publications

References 42 publications

Early Phase Mast Cell Activation Determines the Chronic Outcome of Renal Ischemia–Reperfusion Injury

Early Phase Mast Cell Activation Determines the Chronic Outcome of Renal Ischemia–Reperfusion Injury

The controversial role of mast cells in fibrosis

Delayed Rectifier K⁺-Channel Is a Novel Therapeutic Target for Interstitial Renal Fibrosis in Rats with Unilateral Ureteral Obstruction

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Less contribution of mast cells to the progression of renal fibrosis in Rat kidneys with chronic renal failure

Cited by 6 publications

References 42 publications

Early Phase Mast Cell Activation Determines the Chronic Outcome of Renal Ischemia–Reperfusion Injury

Early Phase Mast Cell Activation Determines the Chronic Outcome of Renal Ischemia–Reperfusion Injury

The controversial role of mast cells in fibrosis

Delayed Rectifier K+-Channel Is a Novel Therapeutic Target for Interstitial Renal Fibrosis in Rats with Unilateral Ureteral Obstruction

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Product

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Delayed Rectifier K⁺-Channel Is a Novel Therapeutic Target for Interstitial Renal Fibrosis in Rats with Unilateral Ureteral Obstruction