Int J Med Sci
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Wnt signaling is relevant for a wide range of biological processes, including reproductive function. The function of Wnt10a in female fertility, however, remains obscure. In the present study, we explored the structure and function of the female reproductive organs in Wnt10a knockout (KO) mice. ⋯ The expression of the ovarian cytochrome P450 family 19 subfamily A member 1 (Cyp19a1) was significantly lower in Wnt10a KO mice. We detected no significant changes in the levels of the gonadotropins between WT and KO mice. Together, our findings indicate that deficiency of Wnt10a causes female infertility through β-catenin and Cyp19a1signaling pathways in mice.
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Background and aims: The miRNA-based post-transcription modification has been extensively studied in hypertension. It however remains elusive how miRNA expression is regulated in this pathological process. We hypothesize that hydroxymethylation in the promoter regions tightly controls the levels of key miRNAs, which in turn affects the development of hypertension. ⋯ Conclusions: Our study suggested that hydroxymethylation in the promoter regions controlled the level of miR-3571 and revealed the important roles of miR-3571 and CLDN1 in VSMCs during the development of hypertension. In addition, our results also indicated that miR-3571/CLDN1 axis regulated the functions of VSMCs via the ERK1/2 pathway. Taken together, our findings support miR-3571 as a novel biomarker for the diagnosis and prevention of hypertension.
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Sepsis, which is a serious medical condition induced by infection, has been the most common cause of acute kidney injury (AKI) and is associated with high mortality and morbidity. Sodium-glucose cotransporter 2 (SGLT2) inhibitor is a new oral antidiabetic drug that has greatly improved the cardiovascular and renal outcomes in patients with type 2 diabetes independent of its sugar lowering effect, possibly by attenuation of the inflammatory process. We investigated the effect of the SGLT2 inhibitor dapagliflozin on lipopolysaccharide (LPS)-induced endotoxic shock with AKI in streptozotocin-induced diabetic mice. ⋯ Treatment with dapagliflozin attenuated LPS-induced endotoxic shock associated AKI and decreased the inflammatory cytokines in diabetic mice. In the in vitro study, dapagliflozin decreased the expression of inflammatory cytokines and reactive oxygen species and increased the expressions of AMP-activated protein kinase (AMPK), nuclear factor erythroid-2-related factor, and heme oxygenase 1. These results demonstrated that dapagliflozin can attenuate LPS-induced endotoxic shock associated with AKI; this was possibly mediated by activation of the AMPK pathway.
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Background: ECM proteins are instrumental for angiogenesis, which plays momentous roles during development and repair in various organs, including post cardiac insult. After a screening based on an open access RNA-seq database, we identified Nephronectin (NPNT), an extracellular protein, might be involved in cardiac repair post myocardial infarction (MI). However, the specific impact of nephronectin during cardiac repair in MI remains elusive. ⋯ The migration and capillary-like tube formation events could be readily revoked by EGFR or STAT3 inhibition. Notably, phosphorylation of EGFR, JAK2 and STAT3 were markedly upregulated in AAV2/9-cTnT-NPNT-treated mice with MI. Conclusions: Our study thus identifies the beneficial effects of NPNT on angiogenesis and cardiac repair post MI by enhancing the EGFR/JAK2/STAT3 signaling pathway, implying the potential therapeutic application of NPNT on myocardial dysfunction post MI.
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Pulmonary arterial hypertension (PAH) characterized by pulmonary vascular remodeling is a lethal disease. Paeoniflorin (PF) is a monoterpene glycoside with numerous beneficial functions, such as vasodilation, anti-inflammation and immunomodulation. This study aims to investigate the effects of PF on monocrotaline (MCT)-induced PAH rats. ⋯ PF also partially reversed TGFβ1, interleukin-1β (IL-1β) and tumor necrosis factor (TNF-α) co-stimulated endothelial-to-mesenchymal transition (EndMT) in cultured human pulmonary artery endothelial cells (HPAECs). Signaling pathway analysis demonstrated that the underlying mechanism might be associated with the inhibition of TAK1-MAPK/NF-κB pathways. Taken together, our results suggested that PF could be a potential drug for the treatment of PAH.