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Published on: August 23, 2024
Morphine induces albuminuria by compromising podocyte integrity.
Xiqian Lan1, Partab Rai, Nirupama Chandel
1Renal Molecular Research Laboratoy, Feinstein Institute for Medical Research, Hofstra North Shore LIJ Medical School, Great Neck, New York, USA.
Morphine harms kidney filtration by damaging podocytes and reducing slit diaphragm molecules. This study reveals morphine
Area of Science:
- Nephrology
- Pharmacology
- Cell Biology
Background:
- Chronic kidney disease (CKD) progression is linked to morphine use.
- The effect of morphine on the glomerular filtration barrier, particularly the slit diaphragm (SD), remains largely unknown.
- Podocyte integrity is crucial for maintaining kidney filtration function.
Purpose of the Study:
- To investigate the impact of morphine on the glomerular filtration barrier.
- To specifically examine morphine's effects on podocyte integrity and slit diaphragm molecules (SDCM).
Main Methods:
- In vivo studies: Mice treated with morphine or saline, followed by urine collection and kidney analysis (immunohistochemistry, Western blot).
- In vitro studies: Human podocytes treated with morphine, followed by analysis of SD markers.
- Exploration of receptor pathways (opiate mu and kappa) and signaling pathways (AKT, p38, JNK) involved.
Main Results:
- Morphine administration led to increased albuminuria and podocyte foot process effacement in mice.
- Expression of synaptopodin and SDCM (nephrin, podocin, CD2AP) was significantly decreased in podocytes exposed to morphine, both in vivo and in vitro.
- Morphine-induced reduction in SDCM was mediated by opiate receptors (MOR, KOR), oxidative stress, and signaling pathways (AKT, p38, JNK).
Conclusions:
- Morphine compromises the integrity of the glomerular filtration barrier.
- Morphine alters podocyte structure and function by downregulating key slit diaphragm molecules.
- These effects are mediated through opiate receptors, oxidative stress, and specific intracellular signaling pathways, contributing to kidney damage.
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