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

Yang,Qingmei; Fu,Chensheng; Zhang,Xiaoli; Zhang,Zhenxing; Zou,Jianan; Xiao,Jing; Ye,Zhibin

doi:10.3892/ijmm.2019.4072

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

Authors:
- Qingmei Yang
- Chensheng Fu
- Xiaoli Zhang
- Zhenxing Zhang
- Jianan Zou
- Jing Xiao
- Zhibin Ye
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Affiliations: Department of Nephrology, Huadong Hospital Affiliated with Fudan University, Shanghai 200040, P.R. China
Published online on: January 21, 2019 https://doi.org/10.3892/ijmm.2019.4072
Pages: 1542-1552

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Abstract

Adiponectin (APN) exerts anti‑inflammatory effects in various cells. Uric acid (UA) induces inflammation in proximal renal tubular epithelial cells (PTECs). It remains unknown whether APN protects against UA‑induced inflammation. In the present study, human PTECs were incubated with 100 µg/ml soluble (S) UA in the presence or absence of globular (g) APN, APN receptor 1 (AdipoR1)‑short hairpin RNA lentivirus or compound C. Reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR) assays were performed to assess APN mRNA expression. Immunoblotting was used to assess the protein expression of APN, AdipoR1, NACHT, leucine rich repeat and pyrin domain‑containing protein 3 (NLRP3) and the activation of tumor necrosis factor (TNF) α and adenosine monophosphate‑activated protein kinase (AMPK). ELISA analyses were performed to assess supernatant levels of interleukin (IL)‑1β and TNFα. It was observed that SUA significantly enhanced APN mRNA and protein expression (both P<0.05) and increased NLRP3 (P<0.001) and TNFα (P<0.05) protein levels, as well as supernatant levels of IL‑1β (P<0.01) and TNFα (P<0.001) compared with untreated cells. gAPN administration significantly limited TNFα synthesis and secretion (both P<0.001), significantly decreased IL‑1β release (P<0.01), impacted NLRP3 protein expression and augmented AdipoR1 protein (P<0.01) and AMPK phosphorylation (P<0.05) levels compared with SUA‑treated cells. AdipoR1 knockdown significantly promoted the synthesis (P<0.05) and release of TNFα (P<0.001), significantly increased IL‑1β supernatant levels (P<0.01) and exhibited little influence on NLRP3 production (P>0.05) compared with the SUA‑treated cells. Secreted TNFα levels were significantly increased upon the inhibition of AMPK (P<0.05) and protein levels of IL‑1β, NLRP3 and TNFα in cell lysates were not significantly affected (P>0.05). In summary, the data demonstrated that SUA promoted APN expression in PTECs and that gAPN attenuated SUA‑induced inflammation through the AdipoR1/AMPK signaling pathway. AdipoR1 knockdown and AMPK inactivation increased SUA‑induced inflammatory damage in PTECs. These findings may help to further understand and regulate UA‑associated inflammation in proximal renal tubules.

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