FK506 inhibits the mice glomerular mesangial cells proliferation by affecting the transforming growth factor-βand Smads signal pathways

Abstract

TGF-b1 plays an important role in the pathogenesis of chronic renal diseases. Although the specific mechanism is unknown, a major factor is the potent fibrogenic activity of TGF-b1 in the chronic progression of renal diseases. TGF-b1 closely correlates with renal fibrosis in cooperation with several fibrosis-promoting molecules. Recently it has been studied that, Smad proteins as intracellular mediators of TGF-b signaling pathways provide important insights into the mechanisms determining the specificity of TGF-b action in various renal cells. Some studies have proved that immunosuppressants can affect TGF-b expression, but the mechanisms are unclear. In this study, we investigated the effect of FK506 on mesangial cells via TGF-b and Smads signal pathways. Our results shows that FK506 effectively blocked the TGF-b/Smad signaling pathway by downregulation of TGF-b receptor, and played an important role in TGF-b1-induced Smad2 expression in mice mesangial cells. FK506 can inhibit the TGF-b1-stimulated cell proliferation via Smad-related pathways. And reduced the Smad2 protein and mRNA expression. Altogether, this study provided a theoretical proof for the protective and treating effect of FK506 on kidneys.

Role of MiR-30a in cardiomyocyte autophagy induced by Angiotensin II

“…It can determine cellular survival, together with apoptosis and necrosis. 4,5 Autophagy activity levels are very low in physiological conditions, and it is upregulated in many pathophysiological processes. 6,7 Because cardiomyocytes are terminallydifferentiated cells that cannot divide again, suitable autophagy is essential for the maintenance of cardiomyocyte homeostasis.…”

The efficacy and mechanism of dexmedetomidine in myocardial apoptosis via the renin–angiotensin–aldosterone system

“…There are very limited data available describing the impact of dexmedetomidine on patients with myocardial damage induced by grave scald or burn. 16,17 In contrast, for specific patient populations such as patients with myocardial damage induced by grave scald or burn, relative slowing of the heart rate may be beneficial. Our studies demonstrated that dexmedetomidine could step down HR within the normal range, compared with the simple scald group, which indicated that dexmedetomidine could prevent the heart from the damage of shock heart induced by scalding.…”

Bone Morphogenetic Protein–Based Therapeutic Approaches

“…Although much of the research thus far has focused on BMP-7, it should be noted that other strategies aimed at generally increasing BMP signal transduction have been reported to be beneficial in models of tissue fibrosis. These include administration of recombinant BMP-2 or gene therapy-based BMP-2 expression (Yang et al 2009;Wang et al 2012b), administration of a BMP-related peptide (Sugimoto et al 2012) or the small molecule FK506 (Qi et al 2014), reducing expression of the BMP antagonist gremlin using siRNA (Zhang et al 2010), or delivery of the downstream BMP target genes Id1 and Id3 (Saika et al 2006).…”