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Metformin alleviates lung-endothelial hyperpermeability by regulating cofilin-1/PP2AC pathway
Conclusion: Together, these data reveal the unprecedented endothelial cofilin-1/PP2AC signaling axis downstream of metformin in protecting against lung vascular endothelial injury and inflammation. Therefore, pharmacologically enhancing endothelial PP2AC activity may lead to the development of novel therapeutic approaches for prevention of deleterious effects of ALI on vascular ECs.
Source: Frontiers in Pharmacology - June 8, 2023 Category: Drugs & Pharmacology Source Type: research

Metformin attenuates fibroblast activation during pulmonary fibrosis by targeting S100A4 via AMPK-STAT3 axis
In this study, MET blocked α-smooth muscle actin (α-SMA) accumulation in vivo accompanied with S100A4 expression and STAT3 phosphorylation inhibition, resulting in attenuating the progression of lung fibrosis after BLM administration. We determined that S100A4 plays critical roles in fibroblasts activation in vitro, evidenced by siRNA knockdown of S100A4 expression downregulated TGF-β1 induced α-SMA production in Human fetal lung fibroblast (HFL1) cells. Importantly, we found for the first time that the expression of S100A4 in fibroblasts was regulated by STAT3. Stattic, an effective small molecule inhibitor of STAT3 p...
Source: Frontiers in Pharmacology - February 3, 2023 Category: Drugs & Pharmacology Source Type: research

Effects of metformin on Sonic hedgehog subgroup medulloblastoma progression: In vitro and in vivo studies
Metformin is a first-line drug for type 2 diabetes, and its anticancer effects have also been widely studied in recent years. The Sonic hedgehog (Shh) signaling pathway is involved in the initiation and progression of medulloblastoma. In order to develop a new treatment strategy for medulloblastoma (MB), this study investigated the inhibitory effect of metformin on MB and the underlying mechanism of metformin on the Shh signaling pathway. The effect of metformin on proliferation was evaluated by the cell counting kit-8 (CCK-8) test and colony formation experiment. The effect of metformin on metastasis was assessed by the s...
Source: Frontiers in Pharmacology - October 7, 2022 Category: Drugs & Pharmacology Source Type: research

Metformin Improves the Senescence of Renal Tubular Epithelial Cells in a High-Glucose State Through E2F1
In this study, we explored whether metformin improves a high-glucose-induced senescence and fibrosis of renal tubular epithelial cells through cell cycle-related protein E2F1. In the in vivo experiments, the recombinant adeno-associated virus (AAV-shE2F1) knockdown E2F1 gene was injected into the tail vein of 16-weeks-old db/db mice for 8 weeks. The 16-week-old db/db mice were administered metformin (260 mg/kg/d) continuously for 8 weeks. The normal control group (NC) and diabetic model group (DM) were set up simultaneously. Mice renal tubular epithelial cells (mRTECs) were cultured in vitro. The cells were randomly div...
Source: Frontiers in Pharmacology - June 23, 2022 Category: Drugs & Pharmacology Source Type: research

Acute Administration of Metformin Protects Against Neuronal Apoptosis Induced by Cerebral Ischemia-Reperfusion Injury via Regulation of the AMPK/CREB/BDNF Pathway
Metformin is a first-line anti-diabetic agent with a powerful hypoglycemic effect. Several studies have reported that metformin can improve the prognosis of stroke patients and that this effect is independent of its hypoglycemic effect; however, the specific mechanism remains unclear. In this research, we explored the effect and specific mechanism of metformin in cerebral ischemia-reperfusion (I/R) injury by constructing a transient middle cerebral artery occlusion model in vivo and a glucose and oxygen deprivation/reoxygenation (OGD/R) model in vitro. The results of the in vivo experiments showed that acute treatment with...
Source: Frontiers in Pharmacology - April 1, 2022 Category: Drugs & Pharmacology Source Type: research

Metformin Mitigates Cartilage Degradation by Activating AMPK/SIRT1-Mediated Autophagy in a Mouse Osteoarthritis Model
Chondrocyte dysfunction is a key mechanism underlying osteoarthritis. Metformin has shown protective effects in many diseases. The present study aimed to investigate the effects of metformin on autophagy and apoptosis in the process of osteoarthritis. A mouse osteoarthritis model was set up by surgically destabilizing medial meniscus in the knee. Intraarticular injection of metformin or vehicle was applied in the right knee for eight weeks. Mouse articular chondrocytes were isolated and passaged for in vitro experiments. Small interfering RNA (siRNA) transfection was used to silence target genes. Western blotting, immunohi...
Source: Frontiers in Pharmacology - July 23, 2020 Category: Drugs & Pharmacology Source Type: research