Tamsulosin attenuates high glucose- induced injury in glomerular endothelial cells

Abstract

Diabetic nephropathy (DN) is a common complication of diabetes. Tamsulosin is a selective α1-AR antagonist. α1-AR is expressed widely in kidney tissues and has displayed its various physiological functions. However, whether Tamsulosin has affects DN is unknown. To our knowledge, this is the first time it has been examined whether Tamsulosin possesses a beneficial effect in high glucosechallenged glomerular endothelial cells (GECs). Firstly, we found that Tamsulosin reduced high glucose-induced expressions of TNF-α, IL-6, and IL-8. Secondly, Tamsulosin alleviated high glucose-induced expressions of MMP-2 and MMP-9. Thirdly, Tamsulosin inhibited the expressions of VCAM-1 and ICAM-1. Importantly, our results indicate that Tamsulosin inhibited high glucoseinduced expressions of fibrosis factors such as Col-1 and TGF-β1. Additionally, we found that Tamsulosin ameliorated oxidative stress via reducing the generation of ROS and preventing the activation of p38. Mechanistically, we found that Tamsulosin attenuated high glucose-induced activation of NF-κB. Based on these findings, we conclude that Tamsulosin could attenuate high glucose-induced injury in GECs through alleviating oxidative stress and inflammatory response.

Identification and verification of vascular cell adhesion protein 1 as an immune-related hub gene associated with the tubulointerstitial injury in diabetic kidney disease

“…As VCAM1 is an adhesion molecule for lymphocytes and monocytes, the positive correlation between VCAM1 expression and interstitial immune cell infiltration in our study indicated that elevated tubular VCAM1 expression might allow the protein to interact with mononuclear cells, thus promoting interstitial fibrosis. Consistent with our results, an increase in tubular VCAM1 expression in episodes of acute renal allograft rejection is associated with T cell and monocyte infiltration [ 50 ] . In addition, we found a positive correlation between VCAM1 expression and pyroptosis, indicating that pyroptotic tubular cells might release VCAM1.…”

“…Patients with type 2 diabetes present significantly elevated serum levels of VCAM1, and VCAM1 levels correlate well with the extent of albuminuria [ 49 ] . Previous studies on VCAM1 in DKD mainly mainly focused on glomerular endothelial cells [ 50 ] . However, researchers have not completely elucidated whether renal tubular expression of VCAM1 is elevated in patients with DKD and whether it is involved in the interstitial pathogenesis of DKD.…”

The Selective α1 Antagonist Tamsulosin Alters ECM Distributions and Cellular Metabolic Functions of ARPE 19 Cells in a Concentration-Dependent Manner

“…In addition, it is known that α1AR is also expressed within RPE [ 10 ], so we reasonably speculated that the presence of the unidentified TAM induced some effects on RPE. In fact (and quite interestingly), it has been suggested that TAM may induce some favorable effects in RPE cells in diabetic retinopathy (DR) based on a recent study reporting that TAM may induce beneficial effects in diabetic nephropathy (DN) [ 43 ]. These conclusions were supported by the following results: (1) TAM reduced a high glucose-induced expression of TNF-α, IL-6, IL-8, MMP-2 and MMP-9; (2) TAM inhibited the expression of VCAM-1 and ICAM-1, and a high glucose-induced expression of fibrosis factors such as COL-1 and TGF-β1; and (3) TAM reduced oxidative stress by inhibiting the generation of ROS, thus preventing the activation of p38.…”

The protective effects of S14G-humanin (HNG) against lipopolysaccharide (LPS)- induced inflammatory response in human dental pulp cells (hDPCs) mediated by the TLR4/MyD88/NF-κB pathway

“…In brief, treated hPDCs were incubated with 5 μM MitoSox Red at 37°C for 10 min, followed by 3 washes. The images were taken with a fluorescence microscope (KEYENCE, Tokyo, Japan) [ 23 ].…”