Sarcoma protein kinase inhibition alleviates liver fibrosis by promoting hepatic stellate cells ferroptosis.

Liver fibrosis is a type of chronic pathological liver damage involving liver tissue hypoxia and abnormal extracellular matrix deposits. Hepatic stellate cells (HSCs) activation is critical for liver fibrosis. Currently, inhibiting HSCs activation or inducing HSCs ferroptosis is considered an effective strategy for the treatment of liver fibrosis.

Identifying key genes related to the peritubular capillary rarefaction in renal interstitial fibrosis by bioinformatics.

Renal interstitial fibrosis (RIF) is a key feature of progressive chronic kidney disease (CKD), characterized by tubular epithelial cell (TEC) hypoxia and peritubular capillary (PTC) rarefaction. However, the mechanisms underlying these processes remain poorly understood. To address this knowledge gap, we conducted a comparative transcriptome analysis of hypoxic and normoxic HK-2 cells, identifying 572 differentially expressed genes (DEGs).

Role of MMP-2 and CD147 in kidney fibrosis.

Matrix metalloproteinase-2 (MMP-2) and cluster of differentiation 147 (CD147) both play important roles in the development of kidney fibrosis, and CD147 can induce the production and activation of MMP-2. In the early stage of kidney fibrosis, MMP-2 promotes extracellular matrix (ECM) production and accelerates the development of kidney fibrosis, while in the advanced stage, MMP-2 activity decreases, leading to reduced ECM degradation and making it difficult to alleviate kidney fibrosis. The reason for the decrease in MMP-2 activity in the advanced stage is still unclear.

Crocin inhibits the activation of mouse hepatic stellate cells via the lnc-LFAR1/MTF-1/GDNF pathway.

Crocin is the main monomer of saffron, which is a momentous component of traditional Chinese medicine Lang Qing A Ta. Here, we tried to probe into the role of crocin in liver fibrosis. Hematoxylin-eosin staining and Sirius Red staining were used to observe the pathological changes of liver tissues.

Huagan tongluo Fang improves liver fibrosis via down-regulating miR-184 and up-regulating FOXO1 to inhibit Th17 cell differentiation.

Background: The purpose of this research is to reveal the improvement effect and potential mechanism of Huagan tongluo Fang (HGTLF) on liver fibrosis.

Methods: A mouse model of liver fibrosis induced by CCl was established to analyze the effect of HGTLF on liver fibrosis. The expression changes of miRNA after HGTLF stimulation were detected by qRT-PCR.

Rab7 empowers renal tubular epithelial cells with autophagy-mediated protection against albumin-induced injury.

Most patients with chronic kidney disease (CKD) present with proteinuria and extracellular matrix (ECM) deposition in the interstitium. Matrix metalloproteinase-2 (MMP-2) is important for maintaining ECM metabolism and it affects the formation and development of CKD. Autophagy has been reported to be protective against renal tubular injury, but the role of autophagy related to ECM metabolism is unclear.

Effects of Simultaneous Downregulation of PHD1 and Keap1 on Prevention and Reversal of Liver Fibrosis in Mice.

To investigate whether double-knockdown of PHD1 and Keap1 in mice could enhance the resolution of carbon tetrachloride (CCl)-induced liver fibrosis. The liver fibrosis model of mice was established by intraperitoneal injection of 25% CCl in olive oil (4 ul/g) twice a week for 8 weeks. PHD1shRNA and Keap1shRNA eukaryotic expression plasmids were simultaneously administered from the beginning of the first to fourth week (preventive group) or from the fifth to eighth week of CCl injection (therapeutic group) via hydrodynamic-based tail vein injection.

Hypoxia Activates Src and Promotes Endocytosis Which Decreases MMP-2 Activity and Aggravates Renal Interstitial Fibrosis.

The aggravation of renal interstitial fibrosis in the advanced-stage of chronic kidney disease is related to decreased matrix metalloproteinase-2 (MMP-2) activity, which is induced by hypoxia in the kidney; however, the specific mechanism remains unclear. We previously demonstrated that inhibition of Caveolin-1, a key gene involved in endocytosis, increased MMP-2 activity in hypoxic HK-2 cells. It has been reported that activated Src (phospho-Src Tyr416) is a key molecule in multiple fibrotic pathways.

An Attempt to Establish a Common Animal Model for Hepatorenal Fibrosis in Rats.

It is already a proven fact that there exists a relationship between CLD (chronic liver disease) and kidney disease but still there is no available combined animal model of liver and kidney fibrosis on the same animal. An animal model is one of the important research tools in the field of medical science because it is important to build a model that can simulate the disease condition so that the particular disease can be studied. Therefore, the aim of this study is to build a less expensive, less time consuming, and reproducible model of hepatorenal fibrosis on rats.

A modified approach to establish a murine model of hypoxic renal interstitial fibrosis.

Modelling methods that are commonly used to establish a murine model of hypoxic renal interstitial fibrosis mainly includes 5/6 nephrectomy, unilateral ureteral obstruction and cyclosporin A (CsA)-induced renal interstitial fibrosis. The first two methods are technically challenging and unsuitable for clinical practice; thus, CsA induction is more promising. A previously introduced model of CsA-induced renal interstitial fibrosis involves the subcutaneous injection of CsA combined with a 0.

Endothelial cells co-cultured with renal carcinoma cells significantly reduce RECK expression under chemical hypoxia.

Renal cell carcinoma (RCC) is characterized by excessive angiogenesis, while chronic kidney disease (CKD) suffers from the opposite problem-failure of reparative angiogenesis. It can be due to their different responses to hypoxic environment. But the specific molecular regulators are still unclear.

Double Knockdown of PHD1 and Keap1 Attenuated Hypoxia-Induced Injuries in Hepatocytes.

Hypoxia and oxidative stress contribute toward liver fibrosis. In this experiment, we used small hairpin RNA (shRNA) to interfere with the intracellular oxygen sensor-prolyl hydroxylase 1 (PHD1) and the intracellular oxidative stress sensor-kelch-like ECH associated protein 1 (Keap1) in the hypoxic hepatocytes in order to investigate the function of PHD1and Keap1. We first established the CCl-induced liver fibrosis model, subsequently, the levels of the PHD1, hypoxia-inducible factor-1α (HIF-1α), hypoxia-inducible factor-2α (HIF-2α), Keap1, and nuclear factor-erythroid 2 p45-related factor 2 (Nrf2) were detected in liver tissues.

MMP-2 and 9 in Chronic Kidney Disease.

Gelatinases are members of the matrix metalloproteinase (MMPs) family; they play an important role in the degradation of the extracellular matrix (ECM). This effect is also crucial in the development and progression of chronic kidney disease (CKD). Its expression, as well as its activity regulation are closely related to the cell signaling pathways, hypoxia and cell membrane structural change.

Effects of autophagy and endocytosis on the activity of matrix metalloproteinase‑2 in human renal proximal tubular cells under hypoxia.

Tubulointerstitial fibrosis is characterized by tubular atrophy with basement membrane thickening and accumulation of interstitial extracellular matrix (ECM). A decrease in the activity of matrix metalloproteinase‑2 (MMP‑2) may promote this process. Although proximal tubular cells are sensitive to oxygen deprivation, whether cellular autophagy or endocytosis induced by hypoxia can alter the activity of MMP‑2 remains to be elucidated.

Transcriptomic changes in human renal proximal tubular cells revealed under hypoxic conditions by RNA sequencing.

Chronic hypoxia often occurs among patients with chronic kidney disease (CKD). Renal proximal tubular cells may be the primary target of a hypoxic insult. However, the underlying transcriptional mechanisms remain undefined.

RASAL1 attenuates gastric carcinogenesis in nude mice by blocking RAS/ERK signaling.

Recent studies have suggested that the RAS protein activator like-1 (RASAL1) functions as a tumor suppressor in vitro and may play an important role in the development of gastric cancer. However, whether or not RASAL1 suppresses tumor growth in vivo remains to be determined. In the present study, we investigated the role of RASAL1 in gastric carcinogenesis using an in vivo xenograft model.

RASAL1 influences the proliferation and invasion of gastric cancer cells by regulating the RAS/ERK signaling pathway.

The aim of this study was to investigate the biological characteristics of the RASAL1 gene in a well-differentiated gastric cancer cell line MKN-28 and a poorly differentiated gastric cancer cell line BGC-823 cells, using RNA interference and gene transfection technology, respectively. MKN-28 cells were transfected with the shRNA of RASAL1 and BGC-823 cells were transfected with the pcDNA 3.1 plasmid vector containing RASAL1.

Hypermethylation and clinicopathological significance of RASAL1 gene in gastric cancer.

Background: Recent studies have suggested that expression of the RAS protein activator like-1 gene (RASAL1) is decreased in gastric carcinoma tissues and cell lines, indicated a role in tumorigenesis and development of gastric cancer. Reduced expression of RASAL1 could result in aberrant increase of activity of RAS signaling pathways in cancer cells. However, the exact mechanism which induces down-regulation of the RASAL1 gene remains unclear.