Angiotensin-(1-7) Attenuates Kidney Injury Due to Obstructive Nephropathy in Rats

Kim, Chang Seong; Kim, In Jin; Bae, Eun Hui; Kwon, Seong; Lee, Jong-Un; Kim, Soo Wan

doi:10.1371/journal.pone.0142664

Cited by 50 publications

(36 citation statements)

References 37 publications

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“…Phosphorylated histone H3 is indicative of chromosome condensation during both mitosis and meiosis (manufacturer's information). We observed clear nuclear expression of PHH3 and our staining was consistent with previous reports using this antibody across species including: planaria (Sikes & Newmark, ); zebrafish (Yokokura et al, ) and rats (Kim et al, ).…”

Section: Methodssupporting

confidence: 92%

Neural stem/progenitor cells are activated during tail regeneration in the leopard gecko (Eublepharis macularius)

Gilbert

Vickaryous

2017

J of Comparative Neurology

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As for many lizards, the leopard gecko (Eublepharis macularius) can self-detach its tail to avoid predation and then regenerate a replacement. The replacement tail includes a regenerated spinal cord with a simple morphology: an ependymal layer surrounded by nerve tracts. We hypothesized that cells within the ependymal layer of the original spinal cord include populations of neural stem/progenitor cells (NSPCs) that contribute to the regenerated spinal cord. Prior to tail loss, we performed a bromodeoxyuridine pulse-chase experiment and found that a subset of ependymal layer cells (ELCs) were label-retaining after a 140-day chase period. Next, we conducted a detailed spatiotemporal characterization of these cells before, during, and after tail regeneration. Our findings show that SOX2, a hallmark protein of NSPCs, is constitutively expressed by virtually all ELCs before, during, and after regeneration. We also found that during regeneration, ELCs express an expanded panel of NSPC and lineage-restricted progenitor cell markers, including MSI-1, SOX9, and TUJ1. Using electron microscopy, we determined that multiciliated, uniciliated, and biciliated cells are present, although the latter was only observed in regenerated spinal cords. Our results demonstrate that cells within the ependymal layer of the original, regenerating and fully regenerate spinal cord represent a heterogeneous population. These include radial glia comparable to Type E and Type B cells, and a neuronal-like population of cerebrospinal fluid-contacting cells. We propose that spinal cord regeneration in geckos represents a truncation of the restorative trajectory observed in some urodeles and teleosts, resulting in the formation of a structurally distinct replacement.

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Section: Methodssupporting

confidence: 92%

Neural stem/progenitor cells are activated during tail regeneration in the leopard gecko (Eublepharis macularius)

Gilbert

Vickaryous

2017

J of Comparative Neurology

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“…Because we focused on histological and molecular changes of UUO kidney, we initially did not check the biochemical data such as BUN and serum creatinine level. However, many previous studies have reported that BUN and serum creatinine level was not significantly affected by only ipsilateral UUO due to the presence of a contralateral kidney with good renal function434445464748. Practically, we confirmed normal morphology and histology of contralateral kidney.…”

Section: Discussionsupporting

confidence: 79%

Alpha-lipoic acid ameliorates the epithelial mesenchymal transition induced by unilateral ureteral obstruction in mice

Cho

Kim

Jang

et al. 2017

Sci Rep

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The epithelial-to-mesenchymal transition (EMT) is one of mechanisms that induce renal interstitial fibrosis. Understanding EMT in renal fibrosis has important therapeutic implications for patients with kidney disease. Alpha-lipoic acid (ALA) is a natural compound with antioxidant properties. Studies for ALA are performed in acute kidney injury with renal tubular apoptosis, renal inflammation, and oxidative stress. We investigated the effects of ALA on EMT-mediated renal interstitial fibrosis in mice with unilateral ureteral obstruction (UUO). UUO mice developed severe tubular atrophy and tubulointerstitial fibrosis, with a robust EMT response and ECM deposition after 7 postoperative days. In contrast, ALA-treated UUO mice showed only moderate injury and minimal fibrosis and also larger reductions in the expression of ECM proteins, inflammatory factors, and EMT markers. ALA was shown to be involved in the suppression of infiltrating macrophages associated with EMT and the progression of interstitial fibrosis. It also lessened the destruction of the tubular basement membrane, by reducing the expression of matrix metalloproteinases. This is the first study to show that ALA modulates EMT in a UUO mouse model. Our results suggest that ALA merits further exploration as a therapeutic agent in the prevention and treatment of chronic kidney disease.

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“…and xylazine (5 mg/kg, i.p.) as previous described [Kim et al., ]. Control rats were opened an abdominal cavity, but no ligature was made.…”

Section: Methodsmentioning

confidence: 99%

Tamoxifen ameliorates obstructive nephropathy through Src and the PI3K/Akt/mTOR pathway

Kim

Choi

et al. 2018

Biology of the Cell

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Background information Tubulointerstitial fibrosis is the end‐point of chronic kidney diseases. Tamoxifen, a selective oestrogen receptor (ER) modulator, attenuates renal fibrosis, by regulating the transforming growth factor (TGF)‐β/Smad signalling. Src and phosphoinositide 3‐kinase (PI3K)/Akt pathways play critical roles in the pathogenesis of renal fibrosis. However, the activation of the non‐canonical TGF‐β signalling in renal fibrosis after treatment with tamoxifen remains unclear. Renal fibrosis was induced by unilateral ureteral obstruction (UUO) in rats. Tamoxifen was orally administered after UUO. Additionally, HK‐2 cells were treated with tamoxifen in the presence or absence of TGF‐β1. The selective ER down‐regulator ICI and ER‐α silencing were used to confirm the involvement of ER‐α on the effect of tamoxifen on TGF‐β1‐stimulated fibrosis in HK‐2 cells. Results Tamoxifen treatment ameliorated UUO‐induced renal fibrosis as shown by decreased expression of α‐smooth muscle actin (SMA), fibronectin and connective tissue growth factor (CTGF). The phosphorylation of Src, PI3K, Akt, mammalian target of rapamycin (mTOR) and p70S6K significantly decreased in UUO kidneys from tamoxifen‐treated animals. Tamoxifen dose‐dependently suppressed the TGF‐β1‐induced expression of α‐SMA and CTGF, and phosphorylation of Src, PI3K, Akt, mTOR and p70S6K in HK‐2 cells. These anti‐fibrotic effects were reversed by treatment with ICI and silencing of ER‐α. Moreover, inhibition of the PI3K/Akt and mTOR/p70S6K pathways was observed in HK‐2 cells co‐treated with PP1 (a Src kinase inhibitor) and tamoxifen. Conclusions The anti‐fibrotic effects of tamoxifen are associated with the suppression of Src kinase function via ER‐α, followed by inhibition of the PI3K/Akt and mTOR/p70S6K signalling pathways. Significance Our findings suggest that tamoxifen is a novel therapeutic option for the prevention and treatment of renal fibrosis.

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Angiotensin-(1-7) Attenuates Kidney Injury Due to Obstructive Nephropathy in Rats

Cited by 50 publications

References 37 publications

Neural stem/progenitor cells are activated during tail regeneration in the leopard gecko (Eublepharis macularius)

Neural stem/progenitor cells are activated during tail regeneration in the leopard gecko (Eublepharis macularius)

Alpha-lipoic acid ameliorates the epithelial mesenchymal transition induced by unilateral ureteral obstruction in mice

Tamoxifen ameliorates obstructive nephropathy through Src and the PI3K/Akt/mTOR pathway

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