Adiponectin attenuates Ang Ⅱ‐induced TGFβ1 production in human mesangial cells via an AMPK‐dependent pathway

Abstract

Glomerulosclerosis is a key element in end-stage renal failure. Angiotensin II (Ang II) plays an important role in modulating cell growth and extracellular matrix (ECM) synthesis and degradation. Adiponectin, a protein derived from adipocytes, is primarily involved in regulating glucose levels and fatty acid break down. It has recently been shown to have antiatherosclerotic and anti-inflammatory properties. However, the role of adiponectin as a renoprotective agent has not been fully explored. We herein examine the effect of adiponectin on Ang II-induced TGFβ1 and ECM production in human renal mesangial cells (HRMCs) and explore the signaling pathway involved. In this study, we found that both adiponectin receptor 1 and adiponectin receptor 2 are expressed in HRMCs. Adiponectin (10 μg/mL) attenuated the stimulatory effect of Ang II on TGF-β1 and fibronectin. Furthermore, adiponectin activated the AMP-activated protein kinase (AMPK), and the AMPK-specific inhibitor (compound C) blocked AMPK activation. We also determined that compound C blocked the inhibitory effect of adiponectin on Ang II-stimulated TGFβ1 and fibronectin production. In summary, these results demonstrate that adiponectin suppresses Ang II-induced synthesis of ECM in mesangial cells via activation of the AMPK pathway. Based on our data, we suggest that this mechanism could delay the progression of kidney disease.

Adiponectin protects against uric acid‑induced renal tubular epithelial inflammatory responses via the AdipoR1/AMPK signaling pathway

“…Under conditions of IR, transcription of APN receptor 1 (AdipoR1) (17) and the activation of adenosine monophosphate-activated protein kinase (AMPK) (16) are abolished, decreasing the response sensitivity of APN (16). Over the past two decades, APN has been identified as a potent anti-inflammatory mediator (18)(19)(20)(21)(22) via receptor-dependent mechanisms (23). Various studies indicated that APN is expressed in and acts protectively in renal podocytes (18,24,25), mesangial cells (22,26) and tubular epithelial cells (25,27) in humans and rodents (19,28).…”

“…Over the past two decades, APN has been identified as a potent anti-inflammatory mediator (18)(19)(20)(21)(22) via receptor-dependent mechanisms (23). Various studies indicated that APN is expressed in and acts protectively in renal podocytes (18,24,25), mesangial cells (22,26) and tubular epithelial cells (25,27) in humans and rodents (19,28). It was demonstrated that APN knockout (KO) worsens the severity of kidney structural damage, increases the infiltration of macrophages and upregulates the intrarenal production of proinflammatory factors in subtotal nephrectomized and diabetic mice, whereas the overexpression of APN ameliorated these disorders (22,28).…”

“…Various studies indicated that APN is expressed in and acts protectively in renal podocytes (18,24,25), mesangial cells (22,26) and tubular epithelial cells (25,27) in humans and rodents (19,28). It was demonstrated that APN knockout (KO) worsens the severity of kidney structural damage, increases the infiltration of macrophages and upregulates the intrarenal production of proinflammatory factors in subtotal nephrectomized and diabetic mice, whereas the overexpression of APN ameliorated these disorders (22,28). conversely, few studies argued that APN serves as a proinflammatory factor in the renal tubular cell line HK-2 upon stimulation with lipopolysaccharide (LPS) (29) and in acute kidney injury induced by ischemia-reperfusion (30).…”

Effect of captopril on radiation-induced TGF-β1 secretion in EA.Hy926 human umbilical vein endothelial cells

“…Ang II signaling stimulates TGF-β1 and fibronectin production [32]. In contrast, adiponectin has been shown to attenuate Ang II -induced TGF-β1 production in human mesangial cells via an AMPK-dependent pathway [32]. In this study, TGF-β1 levels in irradiated EA.Hy926 cells increased markedly compared with the control group.…”

“…Studies have indicated that in the early events after radiation, serum and lung TGF-β1 levels were increased [31]. Ang II signaling stimulates TGF-β1 and fibronectin production [32]. In contrast, adiponectin has been shown to attenuate Ang II -induced TGF-β1 production in human mesangial cells via an AMPK-dependent pathway [32].…”