Renal Proximal Tubule Cell-specific Megalin Deletion Does Not Affect Atherosclerosis But Induces Tubulointerstitial Nephritis in Mice Fed Western Diet
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View abstract on PubMed
Summary
This summary is machine-generated.Deleting megalin in kidney proximal tubule cells does not prevent atherosclerosis. Instead, it causes kidney inflammation and damage, particularly in male mice on a Western diet.
Area Of Science
- Nephrology
- Cardiovascular Research
- Molecular Biology
Background
- Megalin (low-density lipoprotein receptor-related protein 2: LRP2) is abundant in renal proximal tubule cells (PTCs).
- Pharmacological inhibition of megalin has previously shown to attenuate atherosclerosis in hypercholesterolemic mice.
Purpose Of The Study
- To investigate if deleting megalin specifically in PTCs reduces atherosclerosis in hypercholesterolemic mice.
Main Methods
- Generated mice with PTC-specific megalin deletion (PTC-LRP2 -/-) on an LDL receptor -/- background.
- Administered a Western diet to induce atherosclerosis and renal pathology.
- Utilized multiphoton microscopy and RNA sequencing for analysis.
Main Results
- PTC-specific megalin deletion did not attenuate atherosclerosis in either sex.
- Male PTC-LRP2 -/- mice on a Western diet developed interstitial CD68+ cell infiltration and tubular atrophy.
- Renal pathologies were diet-dependent, not solely due to hypercholesterolemia, and absent in females.
- Megalin deletion diminished albumin accumulation in PTCs and upregulated kidney inflammation pathways.
Conclusions
- PTC-specific megalin deletion does not impact atherosclerosis.
- It induces diet-dependent tubulointerstitial nephritis, predominantly in male mice.
- This highlights a sex-specific renal response to megalin deficiency under specific dietary conditions.
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