ABSTRACT
Tubulointerstitial fibrosis (TIF) makes a key role in diabetic kidney disease (DKD). In this study, we revealed that the expressions of Egr1 and protease-activated receptor 1 (PAR1) were increased in renal tissues of DKD rats. In vitro experiments demonstrated that both Egr1 overexpression and high glucose (HG) condition could promote the expressions of PAR1, fibronectin (FN) and collagen I (COL I). Furthermore, HG stimulation enhanced the binding capacity of Egr1 to PAR1 promoter. Both HG condition and Egr1 upregulation could increase, and thrombin inhibitor did not affect activity of TGF-ß1/Smad pathway via PAR1. Collectively, Egr1 is involved in TIF of DKD partly through activating TGF-ß1/Smad pathway via transcriptional regulation of PAR1 in HG treated HK-2 cells.
Subject(s)
Receptor, PAR-1 , Transforming Growth Factor beta1 , Rats , Animals , Receptor, PAR-1/genetics , Receptor, PAR-1/metabolism , Transforming Growth Factor beta1/metabolism , Gene Expression Regulation , Fibrosis , Glucose/pharmacologyABSTRACT
The clinical application of gentamicin may lead to acute kidney injury (AKI), and the nephrotoxicity of gentamicin is related to the pathological mechanism of several oxidative and inflammatory cytokines. Plant-derived essential oils have good anti-inflammatory and antioxidant properties. This study aimed to clarify the protective effect of Amomum tsao-ko essential oils (AOs) on gentamicin-induced AKI in rats and its possible mechanism. The rat AKI model was induced by intraperitoneal injection of gentamicin. After 14 days of oral AO treatment, the renal function and pathological changes of the kidney tissues were evaluated, and the level of kidney tissue oxidative stress was detected. The content of inflammatory cytokines was measured by ELISA. The expression of ERK1/2, JNK1/2, p38, NF-κB, caspase-3, and Bax/Bcl-2 proteins were estimated by Western blot analysis. The results showed that taking AO reduced the contents of serum urea and creatinine in AKI rats and improve the pathological changes and oxidative stress of the kidney tissue in rats. At the same time, AO reduced inflammation and apoptosis during AKI by regulating the MAPK pathway. The data show that AO has a protective effect on the kidneys and may be a potential drug for treating kidney injury.
Subject(s)
Acute Kidney Injury , Amomum , Oils, Volatile , Rats , Animals , Gentamicins/adverse effects , Caspase 3/metabolism , MAP Kinase Signaling System , NF-kappa B/metabolism , Creatinine , Antioxidants/pharmacology , bcl-2-Associated X Protein/metabolism , Oils, Volatile/therapeutic use , Acute Kidney Injury/chemically induced , Acute Kidney Injury/drug therapy , Acute Kidney Injury/pathology , Apoptosis , Inflammation/metabolism , Kidney , Signal Transduction , Oxidative Stress , Proto-Oncogene Proteins c-bcl-2/metabolism , Cytokines/metabolism , Anti-Inflammatory Agents/therapeutic use , Urea/pharmacologyABSTRACT
UNLABELLED: Shaneng goat is a famous milking species. Boer goat is world famous goat breed for creophagism. In this study, we evaluated the development potential of adult Boer goat's somatic nuclei after nuclear tansfer (NT) into enucleated MII oocytes of the Shaneng goat. Somatic donor cells were obtained from two different sources: 1) adult granulosa cells (GCs) and 2) adult skin fibroblasts (FCs). The reconstructed embryos that developed to morula or blastocyst stage in vivo were transferred to 38 synchronized recipient. CONTROL: Somatic donor fibroblast cells were obtained from a fetal at 35 day. In the same way the reconstructed embryos were directly transferred to synchronized recipient of Shaneng goats. (1) Experimental group: NT embryos derived from GC and FC developed into morulas and blastocysts at a frequency of 46.8% and 31.4% respectively. Fifty-two NT morula and blastocyst stage embryos were transferred in to 38 recipients, Three of which were confirmed to be pregnant (7.9%). All pregnancies were not maintained to term. (2) CONTROL group: 136 NT embryos were transferred in to 14 recipients, Six of which were confirmed to be pregnant (42.9%). Four of those were maintained to term. Four recipients delivered four male kids (2.9% of embryos transferred). One male kid died at birth, the dead lamb shows as "large offspring syndrome". the others appeared health and normal. DNA analysis confirmed that those kids were genetically identical to their donor. These results demonstrated that Shaneng goat somatic cells could direct normal development and Shaneng goat oocyte cytoplasm supported development of preimplantation embryos produced by NT of somatic cell nuclei from Boer goat.
