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Published on: November 10, 2021
Expression of proinflammatory factors in renal cortex induced by methylmalonic acid
Estibaliz Goyenechea1, Fernando Andrade, Javier de Las Heras
1Division of Metabolism, Cruces University Hospital, Barakaldo, Spain.
Background:
Methylmalonic aciduria is an inborn error of metabolism that causes renal failure and tubulointerstitial (TI) nephritis as complications. This study aimed to examine the levels of expression of several genes related to inflammation, oxidative stress, and mitochondrial function in the renal cortex of rats receiving methylmalonic acid (MMA).
Methods:
Rats received MMA subcutaneously for a month. Tumor necrosis factor alpha (TNFα), nuclear factor-kappa B, interleukin 1 beta (IL-1β), and cyclooxygenase 2 (COX-2) genes were examined by real-time polymerase chain reaction. We also examined transforming growth factor beta (TGF-β) related to TI fibrosis, c-FOS, belonging to the immediate early gene family of transcription factors, and expression of SIRT1, related to energy production.
Results:
There was significantly higher expression of TNFα and a trend toward a higher level of TGF-β transcripts in the methylmalonic model group compared with the controls. However, SIRT1 expression was not different among the groups. Urinary MMA excretion correlated positively with mRNA level of TGF-β. The expression of COX-2 was positively associated with the expression of c-FOS and inversely related to the expression of IL-1β.
Conclusions:
The higher levels of TNFα and TGF-β transcripts suggest inflammation and differentiation processes in the renal cortex in rats because of MMA. After 1 month of MMA injections, expression levels of SIRT1 were not affected, suggesting mitochondrial preservation in early stages of the disease.
Insights
Methylmalonic acid (MMA) exposure in rats increased inflammation and fibrosis gene expression in the kidneys, but early mitochondrial function remained preserved. This suggests potential therapeutic targets for MMA-induced kidney disease.
Area of Science:
- Biochemistry
- Nephrology
- Genetics
Background:
- Methylmalonic aciduria (MMA) is an inherited metabolic disorder.
- Kidney complications include renal failure and tubulointerstitial (TI) nephritis.
- Understanding MMA's renal effects is crucial for disease management.
Purpose of the Study:
- To investigate gene expression changes in the renal cortex of rats exposed to MMA.
- To assess genes involved in inflammation, oxidative stress, and mitochondrial function.
- To explore the relationship between MMA levels and renal gene expression.
Main Methods:
- Rats received subcutaneous methylmalonic acid (MMA) for one month.
- Real-time PCR was used to examine gene expression of TNFα, NF-κB, IL-1β, COX-2, TGF-β, c-FOS, and SIRT1.
- Urinary MMA levels were measured and correlated with gene expression.
Main Results:
- Significantly higher TNFα and a trend for higher TGF-β transcripts were observed in the MMA group.
- Urinary MMA excretion positively correlated with TGF-β mRNA levels.
- SIRT1 expression remained unchanged, indicating preserved mitochondrial function.
Conclusions:
- Elevated TNFα and TGF-β transcripts indicate MMA-induced renal inflammation and differentiation.
- Unchanged SIRT1 expression suggests mitochondrial preservation in early-stage MMA disease.
- These findings highlight potential molecular pathways affected by MMA in the kidney.
