Ramipril can alleviate the accumulation of renal mesangial matrix in rats with diabetic nephropathy by inhibiting insulin-like growth factor-1

Abstract

Purpose To investigate the impact of Ramipril (RAM) on the expressions of insulin-like growth factor-1 (IGF-1) and renal mesangial matrix (RMM) in rats with diabetic nephropathy (DN). Methods The Sprague Dawley rats were divided into normal control (NC) group (n = 12), DN group (n = 11), and DN+RAM group (n = 12). The ratio of renal weight to body weight (RBT), fasting blood glucose (FBG), HbA1c, 24-h urine protein (TPU), blood urea nitrogen (BUN), creatinine (Cr), renal pathological changes, the levels of IGF-1, fibronectin (FN), type IV collagen (Col-IV), and matrix metalloproteinases (MMP)-2 were compared among the groups. Results Compared with NC group, the RBT, FBG, HbA1c, TPU, BUN, Cr, and RMM in DN group were significantly increased (P < 0.05), the IGF-1, FN, and Col-IV were significantly upregulated (P < 0.05), while MMP was significantly downregulated (P < 0.05). Compared with DN group, the indexes except for the FBG and HbA1c in DN+RAM group were significantly improved (P < 0.05), among which IGF-1 exhibited significant positive correlation with TPU(r=0.937), FN(r=0.896) and Col-IV(r=0.871), while significant negative correlation with MMP-2 (r=-0.826) (P<0.05). Conclusion RAM may protect the kidneys by suppressing IGF-1 and mitigating the accumulation of RMM.

Altered DNA methylation of TRIM13 in diabetic nephropathy suppresses mesangial collagen synthesis by promoting ubiquitination of CHOP

“…collagen synthesis and mesangial ECM accumulation. Recently, accumulating studies have identified several agents that alleviate mesangial cell dysfunction in DN, such as perilla frutescent [34], ramipril [35], and daphnetin [36]. TRIM13, as a member of the TRIM superfamily, exerts E3 ubiquitin ligase activity and is involved in multiple cellular processes, including cell apoptosis and survival, differentiation, and tumorigenesis [17].…”

Effect of Dorsomorphin Homolog 1 (DMH1) against Diabetic Dyslipidemia in Streptozotocin-induced Diabetic Rats

“…injection with Streptozotocin (STZ) 60 mg/kg. Three days later, rats with blood glucose level of ≥ 300 mg/dl were considered as diabetics [26] and were randomly divided into three different groups with ten rats each, as the following: Diabetic non-treated group (DC, n = 10) supplemented by regular food and water, Diabetic non-treated group + vehicle (DV, n = 10) injected (i.p.) with equivalent amount of vehicle (12.5% 2-hydroxypropyl-βcyclodextrin [HPβCD]) for 8 weeks, Diabetic treated group (DT, n = 10) injected (i.p.)…”

Ramipril and resveratrol co‐treatment attenuates RhoA/ROCK pathway‐regulated early‐stage diabetic nephropathy‐associated glomerulosclerosis in streptozotocin‐induced diabetic rats

“…Ramipril is a widely used oral ACEi with strong ACE‐inhibitory activity and a prolonged duration of action and should be considered a preferred agent among ACEis . Several studies have shown that ramipril has the potential to alleviate DN in experimental animal models . Moreover, there are no reports investigating whether ACEis affect antioxidative stress signaling pathways following resveratrol treatment or other serious side effects .…”

“…15 Several studies have shown that ramipril has the potential to alleviate DN in experimental animal models. [16][17][18][19] Moreover, there are no reports investigating whether ACEis affect antioxidative stress signaling pathways following resveratrol treatment or other serious side effects. 20 This study investigated the effects of ramipril and resveratrol co-treatment in a rat model of streptozotocin (STZ)-induced DM, which has also been reported as a DN rat model, without hypoglycemic agents or insulin to assess the efficacy of this drug combination on early-stage DN.…”