This study tested the hypothesis that the enhancement of glucagon-like peptide-1 (GLP-1) level through either exogenous supply of GLP-1 agonist, liraglutide or prevention of endogenous GLP-1 degradation with dipeptidyl peptidease-4 inhibitor, lingaliptin ameliorates angiotensin II (Ang II)-induced renal fibrosis.
In this study, we investigated its effects on renal fibrosis in a rat model of 5/6 Nephrectomy (5/6 N) in vivo and in angiotensin II (Ang II)-treated rat glomerular mesangial cells (HBZY-1) in vitro.
Angiotensin II engagement of angiotensin II type 1 receptor (AT1R) is implicated in fibrogenesis, with AT1R blockers used clinically to attenuate cardiac and renal fibrosis.
In mice, JQ1 alleviated Angiotensin II-induced kidney fibrosis and blocked epithelial-mesenchymal transition (EMT) by altering the expression of EMT-related proteins.
This was validated by restoring Smad7 locally in the kidneys of ACE2 knockout mice to block angiotensin II-induced TGF-β/Smad3-mediated renal fibrosis and NF-κB-driven renal inflammation.
In addition, honokiol (HKL), a major bioactive compound isolated from Magnolia officinalis (Houpo), suppressed AngII-induced renal fibrosis through activating SIRT3-KLF15 signaling.
The mechanism of hypertension-induced renal fibrosis is not well understood, although it is established that high levels of angiotensin II contribute to the effect.
Functionally, we determined that angiotensin II is a causative factor responsible for IL-6 induction in the mouse kidney and that genetic deletion of IL-6 significantly reduced hypertension and key features of CKD, including renal injury and progression to renal fibrosis in angiotensin II-infused mice.
The present study has raised the possibility that (P)RR expressed in the diabetic kidney may play a pathophysiological role in angiotensin I generation and renal fibrosis found in end-stage renal disease.
Our results show that angiotensin II activates the Smad signaling system by TGF-beta-independent processes, in vivo and in vitro, causing renal fibrosis.
Angiotensin II (Ang II) has been shown to be implicated in the development of renal fibrosis in several forms of chronic glomerulonephritides, but the precise mechanisms of its effects remain unclear.