PPARγ and mitophagy are involved in hypoxia/reoxygenation-induced renal tubular epithelial cells injury

Abstract

Renal tubular epithelial cell (RTEC) injury is the main cause and common pathological process of various renal diseases. Mitochondrial dysfunction (MtD) is a pathological process after renal injury. Mitophagy is vital for mitochondrial function. Hypoxia is a common cause of RTEC injury. Peroxisome proliferator-activated receptor γ (PPARγ) is involved in cell proliferation, apoptosis, and inflammation. Previous studies have shown that the low expression of PPARγ might be involved in hypoxia-induced RTEC injury. The present study aimed to investigate the correlation between PPARγ and mitophagy in damaged RTEC in the hypoxia/reoxygenation (HR) model. The results showed that HR inhibited the expression of PPARγ, but increased the expression of LC3II, Atg5, SQSTM1/P62, and PINK1 in a time-dependent manner. Moreover, mitochondrial DNA (mt DNA) copy number, mitochondria membrane potential (MMP) levels, ATP content, and cell viability were decreased in hypoxic RTECs, the expression of SQSTM1/P62 and PINK1, the release of cytochrome c (cyt C), and production of reactive oxygen species (ROS) were increased. Mitochondrial-containing autophagosomes (APs) were detected using transmission election microscope (TEM) and laser scanning confocal microscope (LSCM). Furthermore, PPARγ protein expression was negatively correlated with that of LC3II, PINK1, and the positive rate of RTEC-containing mitochondrial-containing APs (all p < .05), but positively correlated with cell viability, MMP level, and ATP content (all p < .05). These data suggested that PPARγ and mitophagy are involved in the RTEC injury process. Thus, a close association could be detected between PPARγ and mitophagy in HR-induced RTEC injury, albeit additional investigation is imperative.

Keywords:

• PPARγ
• renal tubular epithelial cells
• mitophagy
• hypoxia/reoxygenation

Disclosure statement

All authors declare that there are no conflicts of interest in this work.

Additional information

Funding

This work was supported by the Natural Science Foundation of Guangxi Zhuang Autonomous Region (No. 2017GXNSFDA19808).