Anti‐renal interstitial fibrosis effect of norcantharidin is exerted through inhibition of PP2Ac‐mediated C‐terminal phosphorylation of Smad3

Aim: To reveal the alterations of N6-methyladenosine (m6A) epitranscriptome profile in kidney after unilateral ureteral obstruction in mice. Materials & methods: Total renal m6A and expressions of methyltransferases and demethylases were detected by colorimetric quantification method, real-time PCR and western blot, respectively. Methylated RNA immunoprecipitation sequencing was performed to map epitranscriptome-wide m6A profile. Results: Total m6A levels were time-dependent decreased within 1 week, with the lowest level detected at day 7. A total of 823 differentially methylated transcripts in 507 genes were identified. Specifically, demethylated mRNAs selectively acted on multiple pathways, including TGF-β and WNT. Conclusion: m6A modification has a functional importance in renal interstitial fibrosis during obstructive nephropathy and might be a promising therapeutic target.

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LRG1 Mitigates Renal Interstitial Fibrosis through Alleviating Capillary Rarefaction and Inhibiting Inflammatory and Pro-Fibrotic Cytokines

American Journal of Nephrology ◽

10.1159/000514167 ◽

2021 ◽

pp. 1-11

Author(s):

Ting-Ting Liu ◽

Ran Luo ◽

Yi Yang ◽

Yi-Chun Cheng ◽

Dan Chang ◽

...

Keyword(s):

Renal Fibrosis ◽

Interstitial Fibrosis ◽

Critical Role ◽

Tube Formation ◽

Renal Interstitial Fibrosis ◽

Genetic Ablation ◽

Capillary Rarefaction ◽

Peritubular Capillaries ◽

Renal Tubular

Introduction: Increasing evidence has demonstrated that loss of peritubular capillaries plays a critical role in renal interstitial fibrosis. Leucine-rich α2-glycoprotein-1 (LRG1) has been observed promoting angiogenesis in the ocular disease mouse model and myocardial infarction model. We aimed to explore the role of LRG1 in renal interstitial fibrosis. Methods: We analyzed the expression of LRG1 in the plasma and kidney of CKD patients by ELISA and immunohistochemistry. Relationships between the expression of LRG1 in plasma and kidney and renal fibrosis and inflammation were analyzed. Tube formation assay was used to detect the angiogenesis in the human umbilical vein endothelial cell lines (HUVECs). And real-time PCR was used to detect the mRNA expression of LRG1, inflammatory factors, renal tubular injury indicators, pro-fibrotic cytokines, and CD31. We examined the effects of genetic ablation of LRG1 on renal fibrosis induced by unilateral ureteral obstruction (UUO) mice model at day 7. Results: We demonstrated that the expression of LRG1 in renal tissues and plasma samples was upregulated in CKD patients. And the expression of LRG1 was elevated in human renal tubular epithelial cell line (HK-2) cells in response to the stimulation of TNF-α in vitro, and in kidney after UUO in vivo. The deficiency of the LRG1 gene aggravated renal fibrosis, inflammatory cells infiltration, and capillary rarefaction after UUO. In vitro, LRG1 promoted the tube formation of HUVEC cells. LRG1 inhibits fibronectin secretion induced by TGF-β1 in HK-2 and overexpression of LRG1 in HK-2 cells decreased fibronectin secretion. Conclusion: LRG1 may prevent renal fibrosis by inhibiting the secretion of inflammatory and pro-fibrotic cytokines and promoting angiogenesis.

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Identification of key metabolic changes in renal interstitial fibrosis rats using metabonomics and pharmacology

Scientific Reports ◽

10.1038/srep27194 ◽

2016 ◽

Vol 6 (1) ◽

Cited By ~ 14

Author(s):

Liangcai Zhao ◽

Minjian Dong ◽

Shixian Liao ◽

Yao Du ◽

Qi Zhou ◽

...

Keyword(s):

Interstitial Fibrosis ◽

Metabolic Changes ◽

Renal Interstitial Fibrosis

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Fucoidans from Cucumaria frondosa ameliorates renal interstitial fibrosis via inhibition of PI3K/Akt/NF-κB signaling pathway

Food & Function ◽

10.1039/d1fo03067a ◽

2022 ◽

Author(s):

Zhuo-yue Song ◽

Mengru Zhu ◽

Jun Wu ◽

Tian Yu ◽

Yao Chen ◽

...

Keyword(s):

Protein Kinase ◽

Signaling Pathway ◽

Interstitial Fibrosis ◽

Protein Kinase B ◽

Nuclear Factor Κb ◽

Nuclear Factor ◽

Renal Interstitial Fibrosis ◽

Cucumaria Frondosa

The effects of Cucumaria frondosa polysaccharides (CFP) on renal interstitial fibrosis via regulating phosphatidylinositol-3-hydroxykinase/protein kinase-B/Nuclear factor-κB (PI3K/AKT/NF-κB) signaling pathway were investigated in vivo and in vitro in this research. A...

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FC 044THE LONG-TERM EFFECTS OF ACUTE KIDNEY INJURY ON INTESTINAL OXALATE-DEGRADING BACTERIA IN RATS

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfab119.004 ◽

2021 ◽

Vol 36 (Supplement_1) ◽

Author(s):

Natalia Stepanova ◽

Ganna Tolstanova ◽

Valentyn Nepomnyashchii ◽

Iryna Akulenko ◽

Svitlana Savchenko ◽

...

Keyword(s):

Acute Kidney Injury ◽

Serum Creatinine ◽

Interstitial Fibrosis ◽

Kidney Injury ◽

Fecal Microbiota ◽

Long Term Effects ◽

Renal Interstitial Fibrosis ◽

Degrading Bacteria ◽

Group 1

Abstract Background and Aims Gut microbiota is considered an important factor affecting oxalate handling in the intestine. It has been demonstrated that intestinal oxalate secretion provides a complementary route of excretion, and it becomes more evident when kidney function declines. A diversity of gut oxalate-degrading bacteria (ODB) has been hypothesized to play a role in this process. However, there is a general lack of research on the long-term effects of acute kidney injury (AKI) on ODB and their total oxalate-degrading activity (ODA) in fecal microbiota. In this study, we evaluated whether renal dysfunction could affect intestinal ODB and their total ODA in a rat model of glycerol-induced AKI. Method The Male Wistar rats (200-300 g, n=20) on oxalate-free diet were randomly divided into 2 groups. After 24-h of water deprivation, Group 1 (n=10) received an intramuscular injection of 50% glycerol (10 ml/kg of body weight), and Group 2 (n=10) served as control. The numbers of ODB (incubated in a highly selective Oxalate Medium and determined using culture method) and total fecal ODA were measured after injection on days 7 and 70. The method of redoximetric titration with a KMnO4 solution was adopted to evaluate total ODA in fecal microbiota; the results were expressed as % of oxalate degradation per 0.01 g of feces. Renal injury was assessed by histopathological examination, serum creatinine and daily proteinuria levels after removing the animals from the experiment on day 70. Cortical interstitial fibrosis was measured by computerized image analysis on sections stained with picrosirius red. The median (Me) and the interquartile ranges (Q25; Q75) were calculated and compared using the nonparametric Mann-Whitney test. The Spearman correlation coefficient was used to evaluate association between the examined parameters. Results The obtained results demonstrated: 1) after glycerol injection on day 7, no differences were found in the numbers of ODB and total fecal ODA between the experimental and control groups: 5.9 (5.4-6.0) vs 6.0 (5.4-6.4) CFU/g, p=0.65 and 2.0 (0.1-5.0) vs 2.5 (2.0-9.0) %/0.01g, p=0.24, respectively; 2) after AKI initiation on day 70, the numbers of ODB and total fecal ODA were significantly lower in Group I compared with control Group II (Fig. 1); 3) the higher percentage of renal interstitial fibrosis was, the higher total fecal ODA occurred in the experimental rats (Fig. 2). In addition, the number of ODB in feces in Group 1 had an inverse association with serum creatinine (r=-0.52, p=0.006) and 24-h proteinuria levels (r=-0.86, p<0.0001). Conclusion AKI had the long-term negative effects on the quantitative and qualitative characteristics of ODB in fecal microbiota in rats. Moreover, the results of our study confirmed an increasing trend in total fecal ODA according to the aggravation of renal interstitial fibrosis in rats.

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Precision-Cut Kidney Slices as a Tool to Understand the Dynamics of Extracellular Matrix Remodeling in Renal Fibrosis

Biomarker Insights ◽

10.4137/bmi.s38439 ◽

2016 ◽

Vol 11 ◽

pp. BMI.S38439 ◽

Cited By ~ 7

Author(s):

Federica Genovese ◽

Zsolt S. Kàrpàti ◽

Signe H. Nielsen ◽

Morten A. Karsdal

Keyword(s):

Extracellular Matrix ◽

Collagen Type ◽

Interstitial Fibrosis ◽

Ex Vivo ◽

Collagen Type I ◽

Extracellular Matrix Remodeling ◽

Type I ◽

Matrix Remodeling ◽

Renal Interstitial Fibrosis ◽

Ex Vivo Model

The aim of this study was to set up an ex vivo model for renal interstitial fibrosis in order to investigate the extracellular matrix (ECM) turnover profile in the fibrotic kidney. We induced kidney fibrosis in fourteen 12-week-old male Sprague Dawley rats by unilateral ureteral obstruction (UUO) surgery of the right ureter. The left kidney (contralateral) was used as internal control. Six rats were sham operated and used as the control group. Rats were terminated two weeks after the surgery; the kidneys were excised and precision-cut kidney slices (PCKSs) were cultured for five days in serum-free medium. Markers of collagen type I formation (P1NP), collagen type I and III degradation (C1M and C3M), and α-smooth muscle actin (αSMA) were measured in the PCKS supernatants by enzyme-linked immunosorbent assay. P1NP, C1M, C3M, and α-SMA were increased up to 2- to 13-fold in supernatants of tissue slices from the UUO-ligated kidneys compared with the contralateral kidneys ( P < 0.001) and with the kidneys of sham-operated animals ( P < 0.0001). The markers could also reflect the level of fibrosis in different animals. The UUO PCKS ex vivo model provides a valuable translational tool for investigating the extracellular matrix remodeling associated with renal interstitial fibrosis.

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