Suppressive Mechanisms of Sairei-to on Mesangial Matrix Expansion in Rat Mesangioproliferative Glomerulonephritis

Ono, Takahiko; Liu, Ning; Makino, Toshiaki; Nogaki, Fumiaki; Muso, Eri; Honda, Gisho; Kita, Toru

doi:10.1159/000085059

Cited by 19 publications

(16 citation statements)

References 54 publications

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“…We have previously observed that sairei-to treatment restored tissue SOD activity in experimental MsPGN [13]. In agreement with the previous results, plasma SOD activity was also restored by sairei-to treatment in the present study.…”

Section: Discussionsupporting

confidence: 93%

“…Recently, we have observed that sairei-to had suppressive effects on matrix expansion through the inhibition of macrophage infiltration and the recovery of superoxide dismutase (SOD) activity [13]. Suga et al [14] and Ishii et al [15] reported that an experimental model in rats or mice of peritoneal fibrosis through peritoneal injection of chlorhexidine gluconate (CG) resembled human peritoneal fibrosis in a peritoneal dialysis procedure: increased expressions of collagen, α-smooth muscle actin, and macrophage infiltration were noted in this experimental model.…”

Section: Introductionmentioning

confidence: 99%

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Sairei-to Ameliorates Rat Peritoneal Fibrosis Partly through Suppression of Oxidative Stress

Kitamoto

Kato²,

Sugimoto³

et al. 2010

Nephron Exp Nephrol

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Background: Sairei-to is a herbal prescription originating from traditional Chinese medicine. We conducted an experimental study on rat peritoneal fibrosis to clarify the suppressive mechanisms of sairei-to. Methods: Wistar rats were intraperitoneally injected with chlorhexidine gluconate (CG) every day. Peritoneal specimens were collected after 28 days of CG injection and oral administration of sairei-to. Macrophage infiltration, extracellular matrix accumulation, and angiogenesis were evaluated by immunostaining for ED-1, fibronectin, and CD-31, respectively. To observe oxidative stress in the tissue, 4-hydroxy-2-noneal (HNE) accumulation and plasma levels of superoxide dismutase (SOD) activity were detected. As a candidate of antioxidative components in sairei-to, plasma levels of baicalin were determined by high-performance liquid chromatography. Results: Compared with the disease control group, serum total protein levels were significantly recovered in the sairei-to treatment group. Thickness of the submesothelial compact zone, trichrome-stained area, ED-1-positive cells, fibronectin-staining area, and HNE accumulation were suppressed in the treatment group. Concurrently, decreased plasma levels of SOD activity were recovered by sairei-to treatment. Increased CD-31-positive vessel number and area were also suppressed in the sairei-to group. Baicalin was detected in the plasma samples of the sairei-to group at 0.29 ± 0.11 µg/ml (mean±SEM). Conclusion: These results suggest that sairei-to ameliorates peritoneal fibrosis, partly through suppressing oxidative stress and macrophage infiltration.

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Section: Discussionsupporting

confidence: 93%

Section: Introductionmentioning

confidence: 99%

Sairei-to Ameliorates Rat Peritoneal Fibrosis Partly through Suppression of Oxidative Stress

Kitamoto

Kato²,

Sugimoto³

et al. 2010

Nephron Exp Nephrol

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“…Macromolecular immune complexes are formed in situ and deposited in the mesangial area, leading to mesangial cell proliferation and inflammation [4, 5]. These inflammatory mediators in turn stimulate activation, shrinkage, and proliferation of mesangial cells; release a variety of inflammatory mediators and ECM components [6, 7]; and aggravate inflammation, all of which result in glomerular damages, including damage to the molecular barrier and charge barrier of the filtration membrane, and proteinuria [8].…”

Section: Introductionmentioning

confidence: 99%

miR-34a regulates mesangial cell proliferation via the PDGFR-β/Ras-MAPK signaling pathway

Chen

Liu

Mei

et al. 2014

Cell. Mol. Life Sci.

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The main pathological characteristic of glomerulonephritis is diffuse mesangial cell proliferation. MiR-34a is associated with the proliferation of various organs and cancer cells. However, the role of miR-34a in renal proliferation diseases is not clear. Therefore, this study aimed to elucidate the mechanism of miR-34a in the regulation of renal mesangial cell proliferation. The miR-34a expression level at different time points in an anti-Thy1 mesangial proliferative nephritis rat model was determined by qRT-PCR. The cell proliferation rate and cell cycle changes were measured in the in vitro cultured rat mesangial cells (RMCs). Our results suggested that miR-34a expression was negatively correlated with the degree of cell proliferation in the anti-Thy1 nephritis model. MiR-34a could extend the G0/G1 phase and block cell proliferation in RMCs. Dual-luciferase assay results showed that there were binding sites of miR-34a at 3′-UTR of platelet-derived growth factor receptor-β (PDGFR-β). MiR-34a can inhibit PDGFR-β protein expression at a post-transcriptional level, suppress Ras/MAPK signaling pathways, and down-regulate expression of cell cycle proteins at the G0/G1 phase, such as cyclin D1, CDK4/CDK6. In addition, miR-34a may also inhibit RMC proliferation by directly targeting cyclin E and CDK2. MiR-34a inhibits exogenous stimuli-induced proliferation of mesangial cells. Expression levels of phospho-PDGFR-β and phospho-MEK1 (an important downstream molecule in PDGFR-β-induced signaling pathway) were significantly increased in the anti-Thy-1 nephritis rat model. These results suggest that miR-34a may regulate RMC proliferation by directly inhibiting expressions of PDGFR-β, MEK1, and cell cycle proteins, cyclin E and CDK2.

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“…Previously we have observed the recovery of tissue SODlike activity by saireito treatment in experimental MsPGN without uninephrectomy, 12) and it was suggested that flavonoids, including baicalin, partly suppressed experimental glomerular and peritoneal fibrosis by anti-oxidative effects. 12,21) However, the Thy-1 model without uninephrectomy recovers one month after the induction of glomerulonephritis and is considered an acute mesangioproliferative model.…”

Section: Discussionmentioning

confidence: 90%

“…12,21) However, the Thy-1 model without uninephrectomy recovers one month after the induction of glomerulonephritis and is considered an acute mesangioproliferative model. 22) In a preliminary experiment using irreversible Thy-1 nephritis, saireito suppressed mesangial cell proliferation, but not azotemia (data not shown).…”

Section: Discussionmentioning

confidence: 99%

Protective Effects of Shichimotsu-koka-To on Irreversible Thy-1 Nephritis

Ono

Kamikado

Morimoto

2013

Biological & Pharmaceutical Bulletin

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Oxidative stress and peritubular capillary (PTC) injury are involved in the progression of chronic kidney disease (CKD). We investigated protective effects of Shichimotsu-koka-To (SKT), a Japanese traditional Kampo prescription, against nephrosclerosis and hypertension on a CKD model due to irreversible nephritis. Six-week-old male Wistar rats were subjected to uninephrectomy, and to injection of rabbit anti-thymocyte serum. SKT treatment was continued for 15 weeks, blood pressure was measured, and then renal specimens were collected. PTC networks were detected by immunostaining for CD-31. And superoxide dismutase (SOD)-like activity in the tissue was evaluated. Blood pressure in the SKT group, as well as sham group, was significantly lower than with the vehicle. SKT markedly ameliorated renal function, which was evaluated with urea nitrogen clearance. Compared with the vehicle, SKT treatment lowered both the glomerular enlargement and hyper-cellularity by 80%, and decreased the extracellular matrix area by 75%. SKT treatment also suppressed tubular injury, and maintained PTC networks. Furthermore, SKT recovered SOD-like activity to the basal levels. These results suggest that SKT may be useful for the treatment of CKD during the progression to nephrosclerosis, through the mechanisms of anti-oxidative activity and maintenance of PTC networks.Key words hypertension; glomerular hypertrophy; peritubular capillary; chronic kidney disease; oxidative stressThe number of patients with end-stage renal failure undergoing dialysis is increasing worldwide. Recently, it has been accepted that patients with chronic kidney disease (CKD) also develop cardiovascular diseases, with increased risks of death, cardiovascular events, and hospitalization. 1) Improvement of the clinical outcomes of CKD patients is therefore important. In Japan, chronic glomerulonephritis and nephrosclerosis are major causes of renal failure after diabetic nephropathy, which is the most common cause.2) Hypertension is an important symptom which influences the outcome of CKD, and angiotensin-converting enzyme inhibitors (ACE-Is) and angiotensin II receptor blockers (ARBs) are beneficial to protect against renal injury in CKD.3)The herbal formula Shichimotsu-koka-To (SKT; Table 1) has occasionally been prescribed to treat hypertensive patients. 4)SKT was used for non-obesity hypertensive patients, and those complaining of the sensation of a rush of blood to the head, shoulder stiffness, tinnitus, and dull headache; however, in the last two or three decades, abundant new strong antihypertensive drugs have become available, and SKT has been used less. Recently, reevaluation of SKT treatment in combination with ACE-Is/ARBs drugs in CKD has begun. 5) In basic studies, SKT had an anti-hypertensive effect in Dahl strain rats.6) Enhanced serum NO x levels, and anti-oxidant activity through increasing superoxide dismutase (SOD)-like activity in the kidney by SKT were reported. 7,8) Previously, in a rat model of hypertensive nephrosclerosis induced by 5/6 nephrec...

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Suppressive Mechanisms of Sairei-to on Mesangial Matrix Expansion in Rat Mesangioproliferative Glomerulonephritis

Cited by 19 publications

References 54 publications

Sairei-to Ameliorates Rat Peritoneal Fibrosis Partly through Suppression of Oxidative Stress

Sairei-to Ameliorates Rat Peritoneal Fibrosis Partly through Suppression of Oxidative Stress

miR-34a regulates mesangial cell proliferation via the PDGFR-β/Ras-MAPK signaling pathway

Protective Effects of Shichimotsu-koka-To on Irreversible Thy-1 Nephritis

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