Faculty Opinions recommendation of Endothelial-myofibroblast transition contributes to the early development of diabetic renal interstitial fibrosis in streptozotocin-induced diabetic mice.

2009 ◽  
Author(s):  
Giulio Gabbiani
Keyword(s):  
Early Development ◽  
Interstitial Fibrosis ◽  
Diabetic Mice ◽  
Renal Interstitial Fibrosis

scholarly journals Roscovitine attenuates renal interstitial fibrosis in diabetic mice through the TGF-β1/p38 MAPK pathway

2019 ◽  
Vol 115 ◽  
pp. 108895 ◽  
Author(s):  
Shuo Wang ◽  
Yi Zhou ◽  
Yue Zhang ◽  
Xingyu He ◽  
Xiangning Zhao ◽  
...  
Keyword(s):  
P38 Mapk ◽  
Interstitial Fibrosis ◽  
Mapk Pathway ◽  
Diabetic Mice ◽  
Renal Interstitial Fibrosis ◽  
P38 Mapk Pathway ◽  
Tgf Β1

scholarly journals Mangiferin Alleviates Renal Interstitial Fibrosis in Streptozotocin-Induced Diabetic Mice through Regulating the PTEN/PI3K/Akt Signaling Pathway

2020 ◽  
Vol 2020 ◽  
pp. 1-12 ◽  
Author(s):  
Yanyan Song ◽  
Wei Liu ◽  
Ke Tang ◽  
Junting Zang ◽  
Dong Li ◽  
...  
Keyword(s):  
Body Weight ◽  
Antioxidant Enzymes ◽  
Interstitial Fibrosis ◽  
Morphological Changes ◽  
Fasting Blood Glucose ◽  
Weight Ratio ◽  
Akt Pathway ◽  
Diabetic Mice ◽  
Urine Protein ◽  
Renal Interstitial Fibrosis

Renal interstitial fibrosis is considered to be the typical manifestation of diabetic nephropathy (DN). Mangiferin has shown positive effect on the prevention or treatment of diabetes and its complications. The aim of this study was to explore the inhibitive effect and mechanism of mangiferin on renal interstitial fibrosis in diabetic mice. Streptozotocin- (STZ-) induced diabetic mice were treated with mangiferin (15, 30, and 60 mg/kg/d) for 4 weeks. The morphology of kidneys was observed by Masson’s trichrome staining, and the biochemical parameters (fasting blood glucose (FBG), triglyceride (TG), total cholesterol (TC), blood urea nitrogen (BUN), serum creatinine (SCr), and urine protein) were determined by kits. In addition, the levels of inflammatory cytokines (tumor necrosis factor-α (TNF-α), interleukin- (IL-) 6, and IL-1β), antioxidant enzymes (SOD, CAT, and GSH-Px), MDA, and ROS were assessed. Furthermore, the expressions of fibronectin (FN), collagen I (Col I), and α-SMA were measured by immunohistochemistry. Regulations of TGF-β1 and the PTEN/PI3K/Akt pathway were detected by Western blotting. Treatment with mangiferin significantly ameliorated renal dysfunction in diabetic mice, as evidenced by the increase in body weight and decreases in FBG, TG, TC, BUN, SCr, urine protein, and the kidney to body weight ratio (KW/BW). Furthermore, mangiferin treatment prevented renal interstitial fibrosis evidenced by decreases in the positive expression of FN, Col I, and α-SMA, in comparison with morphological changes in the renal tissue. Meanwhile, mangiferin increased antioxidant enzymes, reduced the TNF-α, IL-6, and IL-1β, as well as MDA and ROS. Additionally, mangiferin administration also downregulated TGF-β1, upregulated PTEN, and decreased the phosphorylation of both PI3K and Akt. These findings demonstrate that mangiferin may reduce inflammation and oxidative stress in DN, thereby inhibiting the renal interstitial fibrosis by reducing the TGF-β1-mediated elevation of Col I, FN, and α-SMA through the PTEN/PI3K/Akt pathway.

scholarly journals HNRNPA1-mediated exosomal sorting of miR-483-5p out of renal tubular epithelial cells promotes the progression of diabetic nephropathy-induced renal interstitial fibrosis

2021 ◽  
Vol 12 (3) ◽  
Author(s):  
DongWei Liu ◽  
FengXun Liu ◽  
ZhengYong Li ◽  
ShaoKang Pan ◽  
JunWei Xie ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Epithelial Cells ◽  
Interstitial Fibrosis ◽  
Diabetic Mice ◽  
Tubular Epithelial Cells ◽  
Renal Interstitial Fibrosis ◽  
Exosomal Sorting ◽  
Type 2 Diabetic

AbstractDiabetic nephropathy (DN) is a serious complication in type 1 and type 2 diabetes, and renal interstitial fibrosis plays a key role in DN progression. Here, we aimed to probe into the role and potential mechanism of miR-483-5p in DN-induced renal interstitial fibrosis. In this study, we corroborated that miR-483-5p expression was lessened in type 1 and type 2 diabetic mice kidney tissues and high glucose (HG)-stimulated tubular epithelial cells (TECs), and raised in the exosomes derived from renal tissues in type 1 and type 2 diabetic mice. miR-483-5p restrained the expressions of fibrosis-related genes in vitro and renal interstitial fibrosis in vivo. Mechanistically, miR-483-5p bound both TIMP2 and MAPK1, and TIMP2 and MAPK1 were bound up with the regulation of miR-483-5p on renal TECs under HG conditions. Importantly, HNRNPA1-mediated exosomal sorting transported cellular miR-483-5p out of TECs into the urine. Our results expounded that HNRNPA1-mediated exosomal sorting transported cellular miR-483-5p out of TECs into the urine, thus lessening the restraint of cellular miR-483-5p on MAPK1 and TIMP2 mRNAs, and ultimately boosting extracellular matrix deposition and the progression of DN-induced renal interstitial fibrosis.

Alteration of N6-methyladenosine epitranscriptome profile in unilateral ureteral obstructive nephropathy

Epigenomics ◽  
2020 ◽  
Vol 12 (14) ◽  
pp. 1157-1173
Author(s):  
Xueyan Li ◽  
Xu Fan ◽  
Xiaoming Yin ◽  
Huajian Liu ◽  
Yi Yang
Keyword(s):  
Western Blot ◽  
Interstitial Fibrosis ◽  
Unilateral Ureteral Obstruction ◽  
Time Dependent ◽  
Obstructive Nephropathy ◽  
Functional Importance ◽  
Renal Interstitial Fibrosis ◽  
Quantification Method ◽  
Promising Therapeutic Target ◽  
Rna Immunoprecipitation

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.

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

2020 ◽  
Vol 97 (2) ◽  
pp. 293-304
Author(s):  
Han‐wen Luo ◽  
Dan‐dan Yin ◽  
Zheng Xiao ◽  
Lu Wen ◽  
Ying‐jun Liao ◽  
...  
Keyword(s):  
Interstitial Fibrosis ◽  
Renal Interstitial Fibrosis

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

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

<b><i>Introduction:</i></b> 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. <b><i>Methods:</i></b> 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. <b><i>Results:</i></b> 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. <b><i>Conclusion:</i></b> LRG1 may prevent renal fibrosis by inhibiting the secretion of inflammatory and pro-fibrotic cytokines and promoting angiogenesis.

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