<p>Branched Chain Amino Acids Protects Rat Mesangial Cells from High Glucose by Modulating TGF-β1 and BMP-7</p>

Abstract

AimBranched-chain amino acids (BCAAs) have been reported owning curative effects in early diabetic nephropathy. However, the mechanisms of its action have not been elucidated. The aim of this study is to investigate the effect of possible mechanism(s) of BCAAs on cultured rat mesangial cells (RMCs).MethodsRMCs were treated with high glucose (30 mmol/L) and BCAAs (10 mmol/L) respectively. Cell proliferation was detected using an MTT assay. Expression of transforming growth factor (TGF)-β1 and gremlin mRNA was detected by semiquantitative reverse-transcription (RT) PCR. TGF-β1 and fibronectin (FN) protein levels were measured using enzyme-linked immunosorbent assays (ELISAs). Gremlin, bone morphogenic protein (BMP)-7, and Smad2/3 proteins were detected by immunofluorescence. Smad1/5/8 and phosphorylated (p)-Smad1/5/8 were detected by Western blotting.ResultsThe proliferation rate of the RMCs in the high glucose group alone was 1.45-times of cells in the CON group, and it was reduced by 32% upon co-treatment with BCAAs. The expression of TGF-β1, gremlin, p-Smd2/3 and FN mRNA or protein in the HG group was higher than that in the CON group. In the BCAAs group, the corresponding levels were lower than that in HG group. The expression of BMP-7 and p-Smad1/5/8 were significantly lower in the HG group than in the CON group. Moreover, the expression of BMP-7 and p-Smad1/5/8 were higher in the BCAAs group than in the HG group.ConclusionBCAAs showed an antidiabetic effect via reducing TGF-β1-Smad2/3 pathway and Gremlin expression and upregulating BMP-7-Smad1/5/8 pathway in rat mesangial cells, consequently lessening ECM deposition in renal tissue.

Profile of plasma free amino acids, carnitine and acylcarnitines, and JAK2v617f mutation as potential metabolic markers in children with type 1 diabetic nephropathy

“…In rat mesangial cells, BCAAs had an anti‐diabetic impact by down‐regulating Gremlin, and transforming growth factor (TGF)‐ β 1‐Smad2/3 pathway expression. Meanwhile enhancing the expressions of the bone morphogenic protein‐7‐Smad1/5/8 pathway resulted in decreased extracellular matrix deposition in renal tissue (Zhang et al, 2019). While some research has shown that branched‐chain amino acids worsen insulin resistance in T1DM patients, other studies have shown that they increase insulin action and signaling mechanisms (Newgard, 2012; Savolainen et al, 2017).…”

Role of Gut Microbiota, Immune Imbalance, and Allostatic Load in the Occurrence and Development of Diabetic Kidney Disease

“…BCAAs are composed of leucine, valine, and isoleucine [ 186 ]. It has been demonstrated that BCAAs possess the ability to hinder the expression of TGF- β in order to mitigate the damage caused by diabetic kidney injury [ 14 ]. A study recently found that administering high quantities of BCAAs prevented kidney weight in mice with DKD, additionally, moderate amounts of BCAAs led to a reduction in TGF- β mRNA and mitigated oxidative stress by activating the TGF- β pathway, thereby lessening the severity of DKD kidney injury.…”

Depiction of Branched-Chain Amino Acids (BCAAs) in Diabetes with a Focus on Diabetic Microvascular Complications

“…Diabetic nephropathy (DN) is a serious microvascular complication of T2DM and the major cause of chronic kidney disease [ 51 ]. It is also a major cause of morbidity and mortality in diabetic patients, as 30 to 40% develop DN [ 52 ]. DN leads to end-stage renal disease, requiring renal replacement therapy such as hemodialysis or kidney transplantation, which determines the necessity of its early detection [ 53 ].…”