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Mechanisms of Macrophage Glycolytic Reprogramming and Interventional Effects of Traditional Chinese Medicine on Renal
Jinwen Xin1, Zhen Chen1, Zilong Yan1
1Department of Nephrology, Shaanxi University of Traditional Chinese Medicine, Xi'an, Shaanxi, People's Republic of China.
Abstract:
Renal fibrosis (RF) is a common pathological outcome of multiple chronic kidney diseases (CKDs), accompanied by substantial extracellular matrix (ECM) deposition and gradual decline of renal function. To date, no clinically viable treatment can reverse progressive renal fibrosis, making it critical to uncover its pathogenic mechanisms. Macrophages display remarkable phenotypic heterogeneity in fibrotic kidneys. Dramatic metabolic reprogramming occurs in these immune cells, with elevated aerobic glycolysis serving as a dominant trait. This metabolic switch not only sustains the energy demand of activated macrophages but also promotes the formation of pro-inflammatory and pro-fibrotic phenotypes. Apart from glycolysis, dysregulated glutaminolysis and lipid metabolism also interact with glycolysis to aggravate renal damage. TCM, owing to its multi-component and multi-target advantages, has shown favorable preclinical effects against renal fibrosis. A growing body of evidence suggests that TCM-derived monomers, formulas, and extracts may exert anti-fibrotic actions by modulating macrophage glycolytic reprogramming. However, the field faces prominent challenges. All relevant data are limited to preclinical studies, with no clinical validation to date. Most research evaluates glycolytic activity indirectly via the expression of metabolic enzymes rather than direct metabolic flux measurement. Additionally, the pharmacokinetics, toxicity, and translational potential of TCM components remain inadequately characterized. This narrative review elaborates the molecular mechanisms of macrophage glycolytic reprogramming in renal fibrosis and summarizes preclinical research on TCM interventions, while clarifying current research deficiencies and future directions.
Insights
Renal fibrosis involves macrophage metabolic reprogramming, specifically increased aerobic glycolysis, which drives kidney damage. Traditional Chinese Medicine (TCM) shows promise in modulating this process, but clinical validation is needed.
Area of Science:
- Immunology
- Metabolism
- Nephrology
Background:
- Renal fibrosis (RF) is a common outcome of chronic kidney diseases (CKDs), leading to kidney function decline.
- Macrophages in fibrotic kidneys exhibit significant metabolic reprogramming, with elevated aerobic glycolysis being a key feature.
- This metabolic shift fuels pro-inflammatory and pro-fibrotic macrophage phenotypes, exacerbating renal damage.
Purpose of the Study:
- To elucidate the molecular mechanisms of macrophage glycolytic reprogramming in renal fibrosis.
- To review preclinical research on Traditional Chinese Medicine (TCM) interventions targeting macrophage metabolism in RF.
- To identify current research gaps and future directions in this field.
Main Methods:
- This narrative review synthesizes existing literature on macrophage metabolism and RF.
- It examines the role of glycolysis, glutaminolysis, and lipid metabolism in kidney fibrosis.
- Preclinical evidence of TCM's effects on macrophage metabolic reprogramming in RF is summarized.
Main Results:
- Elevated aerobic glycolysis in macrophages is a critical driver of pro-inflammatory and pro-fibrotic responses in renal fibrosis.
- Dysregulated glutaminolysis and lipid metabolism further contribute to renal damage.
- Preclinical studies indicate that TCM interventions can modulate macrophage glycolytic reprogramming, showing anti-fibrotic potential.
Conclusions:
- Macrophage metabolic reprogramming, particularly enhanced glycolysis, is a key pathogenic mechanism in renal fibrosis.
- TCM demonstrates preclinical efficacy in targeting these metabolic pathways for anti-fibrotic effects.
- Further research is needed to address limitations, including lack of clinical validation and direct metabolic flux measurements, and to characterize TCM components' pharmacokinetics and toxicity.
