Jinlida granules alleviate podocyte apoptosis and mitochondrial dysfunction via the AMPK/PGC‑1&alpha; pathway in diabetic nephropathy

Sun,Shengnan; Yang,Shurong; Cheng,Ying; Fang,Ting; Qu,Jingru; Tian,Lei; Zhang,Man; Wu,Shi; Sun,Bei; Chen,Liming

doi:10.3892/ijmm.2024.5467

Jinlida granules alleviate podocyte apoptosis and mitochondrial dysfunction via the AMPK/PGC‑1α pathway in diabetic nephropathy

Authors:
- Shengnan Sun
- Shurong Yang
- Ying Cheng
- Ting Fang
- Jingru Qu
- Lei Tian
- Man Zhang
- Shi Wu
- Bei Sun
- Liming Chen
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Affiliations: NHC Key Laboratory of Hormones and Development, Tianjin Key Laboratory of Metabolic Diseases, Chu Hsien‑I Memorial Hospital and Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin 300134, P.R. China
Published online on: December 5, 2024 https://doi.org/10.3892/ijmm.2024.5467
Article Number: 26
Copyright: © Sun et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Traditional Chinese Medicine (TCM) has demonstrated promising efficacy in managing and preventing the early‑stage diabetic nephropathy (DN). Although the exact mechanisms remain elusive, clinical evidence has suggested that Jinlida granules (JLD) are beneficial in improving renal function among patients with DN. The present study aimed to elucidate the effect of JLD on DN and the underlying molecular mechanism. Therefore, podocyte apoptosis was evaluated using flow cytometry and TUNEL staining, while mitochondrial morphology and function were assessed using transmission electron microscopy, MitoTracker, JC‑1 and reactive oxygen species staining. RNA sequencing analysis was performed to elucidate the mechanism underlying the effect of JLD on DN. Additionally, to investigate the role of peroxisome proliferator‑activated receptor‑γ co‑activator‑1α (PGC‑1α) in mitigating JLD‑induced mitochondrial dysfunction and podocyte apoptosis, MPC5 cells were transfected with the corresponding small interfering RNA constructs. The results showed that JLD effectively improved renal function and mitigated podocyte injury, as well as ameliorated mitochondrial dysfunction and inhibited apoptosis in db/db mice. In vitro experiments further revealed that JLD exerted a protective effect via inhibiting mitochondrial fission and apoptosis in high glucose‑treated podocytes. Furthermore, JLD enhanced the phosphorylation of adenosine monophosphate‑activated protein kinase (AMPK), thus promoting the expression of PGC‑1α, eventually improving apoptosis and mitochondrial homeostasis. Overall, the current study revealed that JLD could improve mitochondrial homeostasis and reduce cell apoptosis in podocytes via activating the AMPK/PGC‑1α pathway, thus providing a theoretical foundation for the clinical management of DN.

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