The role of PCSK9 in glomerular lipid accumulation and renal injury in diabetic kidney disease
Authors' conclusion
The downregulation of PCSK9 in podocytes is associated with lipid accumulation, which leads to mitochondrial dysfunction, cell apoptosis and renal injury. This study sheds new light on the potential involvement of PCSK9 in the pathophysiology of glomerular lipid accumulation and podocyte injury in DKD.
Study context
- Population
- Human kidney biopsy glomeruli from individuals with diabetic kidney disease (DKD); db/db and db/m mice; C57BL/6 and Pcsk9 knockout (KO) mice with induced DKD; immortalised mouse podocytes under diabetic conditions
- Comparison
- Pcsk9 KO vs wild-type (WT) DKD mice; PCSK9 overexpression vs knockdown in podocytes
- Outcome
- Role of intracellular PCSK9 in glomerular lipid accumulation and podocyte injury in DKD
Methodological detailshuman kidney biopsy glomerular gene expression, db/db and db/m mice, Pcsk9 KO DKD mouse model (high-fat diet + low-dose streptozocin), conditionally immortalised mouse podocytes (lentivirus overexpression, siRNA knockdown)
- Human kidney biopsy glomerular gene expression
- Db/db and db/m mice
- Pcsk9 KO DKD mouse model (high-fat diet + low-dose streptozocin)
- Conditionally immortalised mouse podocytes (lentivirus overexpression, siRNA knockdown)
Main finding
As reported in the abstract
- Significant reduction in PCSK9 transcription in glomeruli of individuals with DKD
- PCSK9 expression reduced in podocytes of animals under diabetic conditions
- Significantly higher lipid accumulation in kidney tissues of Pcsk9 KO DKD vs WT DKD mice
- Significant reduction in mitochondria number, with significant increase in mitochondrial size, in Pcsk9 KO vs WT DKD models
- Albuminuria and podocyte foot process effacement in WT and Pcsk9 KO DKD mice, more pronounced in KO
- In podocytes exposed to diabetic stimuli, heightened lipid accumulation, mitochondrial injury and apoptosis were ameliorated by Pcsk9 overexpression and aggravated by Pcsk9 knockdown
Original publication
The role of PCSK9 in glomerular lipid accumulation and renal injury in diabetic kidney disease. Diabetologia. Published 15 June 2024. doi:10.
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