Shenkang Injection (SKI) is a traditional Chinese medicine injection commonly used in the clinical treatment of chronic kidney disease. Although it has been confirmed that SKI has anti-kidney fibrosis effects, the underlying mechanism remains unclear. To investigate the effects of SKI on epithelial-mesenchymal transition (EMT) and Wnt/β-catenin pathway and explore its potential anti-fibrosis mechanism. A unilateral ureteral obstruction (UUO) model was induced by ligating the left ureter of male SD rats. A total of 24 rats were randomly divided into the following four groups: sham group, model group, SKI group, and benazepril group. The rats in each group were treated for 28 days, and renal function was evaluated by blood urea nitrogen (BUN) and serum creatinine (Scr). The degree of renal fibrosis was assessed by hematoxylin and eosin (HE) and Masson staining. Extracellular matrix (ECM) deposition was evaluated by immunohistochemistry. Real-time fluorescent quantitative PCR (RT-qPCR) and western blotting were used to detect the expression of genes and proteins in the Wnt/β-catenin signaling pathway. Further studies were performed in vitro using HK-2 cells treated with TGF-β1. At 28 days postoperation, the levels of BUN and Scr expression were significantly increased in the UUO group. SKI and benazepril reduced the levels of BUN and Scr, which displayed protective renal effects. Pathological staining showed that compared with the sham operation group, the renal parenchymal structure was severely damaged, the number of glomeruli was reduced, and a large amount of collagen was deposited in the kidney tissue of the UUO group. SKI treatment reduced morphological changes. Immunohistochemistry showed that compared with the sham operation group, the content of collagen I and FN in the kidney tissue of the UUO group were significantly increased, whereas the SKI content was decreased. In addition, compared with the UUO group, the levels of Wnt1, active β-catenin, Snail1, and PAI-1 expression were reduced in the SKI group, suggesting that SKI may reduce renal fibrosis by mediating the Wnt/β-catenin pathway. Further in vitro studies showed that collagen I, FN, and α-SMA levels in HK-2 cells were significantly increased following stimulation with TGF-β1. SKI could significantly reduce the expression of collagen I, FN, and α-SMA. A scratch test showed that SKI could reduce HK-2 migration. In addition, by stimulating TGF-β1, the levels of Wnt1, active β-catenin, snail1, and PAI-1 were significantly upregulated. SKI treatment could inhibit the activity of the Wnt/β-catenin signaling pathway in HK-2 cells. SKI improves kidney function by inhibiting renal fibrosis. The anti-fibrotic effects may be mediated by regulation of the Wnt/β-catenin pathway and EMT inhibition.
Chronic kidney disease (CKD) is a major public health problem that affects more than 10% of the population worldwide and has a high mortality rate. Therefore, it is necessary to identify novel treatment strategies for CKD. Incidentally, renal fibrosis plays a central role in the progression of CKD to end-stage renal disease (ESRD). The activation of inflammatory pathways leads to the development of renal fibrosis. In fact, interleukin-33 (IL-33), a newly discovered member of the interleukin 1 (IL-1) cytokine family, is a crucial regulator of the inflammatory process. It exerts pro-inflammatory and pro-fibrotic effects via the suppression of tumorigenicity 2 (ST2) receptor, which, in turn, activates other inflammatory pathways. Although the role of this pathway in cardiac, pulmonary, and hepatic fibrotic diseases has been extensively studied, its precise role in renal fibrosis has not yet been completely elucidated. Recent studies have shown that a sustained activation of IL-33/ST2 pathway promotes the development of renal fibrosis. However, with prolonged research in this field, it is expected that the IL-33/ST2 pathway will be used as a diagnostic and prognostic tool for renal diseases. In addition, the IL-33/ST2 pathway seems to be a new target for the future treatment of CKD. Here, we review the mechanisms and potential applications of the IL-33/ST2 pathway in renal fibrosis; such that it can help clinicians and researchers to explore effective treatment options and develop novel medicines for CKD patients.
Systemic lupus erythematosus (SLE) is one of the complex disorders in human beings. It is characterized by much production of autoantibodies, which deposit in organs, such as the kidney. 1 Lupus nephritis (LN) is a characteristic complication in SLE, where there is a dysregulated inflammatory environment in the kidney.Excessive inflammatory cell infiltration, pro-inflammatory cytokines and chemokines accumulation promote a series of damages in the kidney, such as fibrosis. Finding out the reasons related to kidney damage in lupus, and targeting the damage is good for reversing lupus.Being a member of the tumor necrosis factor (TNF) ligand family, TNF-like weak inducer of apoptosis (TWEAK) is a multifunctional pro-inflammatory cytokine. It was first described as an inducer of apoptosis in transformed cell lines, 2 then, it was reported to correlate with a pathogenic role in inflammation. Human TWEAK gene was located at chromosome 17p13.1, which encoded a 249 amino acid type II transmembrane glycoprotein with 30 kD. TWEAK is expressed in different immune cells, tissues, organs, such as monocytes, dendritic cells, T cells as well as heart, colon and kidney. 3 Fibroblast growth factor-inducible 14 (Fn14) is the only receptor for TWEAK. Fn14 is expressed in a variety of resident cells, especially under inflammatory conditions. 4,5 TWEAK binds to Fn14, activates
Skin cutaneous melanoma (SKCM) is a disease with the highest mortality rate among skin cancers. As a new type of programmed cell death, ferroptosis has been confirmed to be related to the occurrence and development of a variety of cancers. At present, the expression and prognostic value of ferroptosis-related genes (FRGs) in SKCM are still unclear. In this study, we selected seven FRGs that were differentially expressed in SKCM and related to the patient’s prognosis through the databases. Further studies have shown that these genes are closely related to immune cell infiltration and immune checkpoints. All in all, these seven FRGs may be potential targets for clinical diagnosis, prognosis and treatment of SKCM patients.
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