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Updated: Mar 19, 2026
Rapid Depletion of Renal Macrophages Using Human CD59/Intermedilysin Cell Ablation Tool
Published on: May 9, 2025
Macrophage RNA polymerase II subunit 5-mediating protein deficiency exacerbates kidney inflammation and fibrosis
Jiayi Nie1, Benquan Liu1, Heng Xiong1
1Department of Anesthesiology, Affiliated Foshan Women and Children Hospital, Guangdong Medical University, Foshan, 528000, China.
Background:
Chronic kidney disease is closely associated with kidney inflammation and fibrosis. Macrophage plays a critical role in the pathogenesis of kidney inflammation and fibrosis. However, the molecular mechanisms underlying macrophage activation remain poorly elucidated. In this work, we examined the role of macrophage RNA polymerase II subunit 5 -mediating protein (RMP) in kidney inflammation and fibrosis.
Methods:
The mouse model of kidney fibrosis was induced by folic acid administration or unilateral ureteral obstruction . Macrophage-specific RMP knockout mice and wild-type controls were subjected to folic acid or obstructive injury. Macrophages derived from wild-type or RMP deficiency mice were exposed to TGF-β1 stimuli. Kidney collagen deposition, extracellular matrix protein expression, macrophage to myofibroblast transition, and inflammatory cytokines were assessed using histological staining, Western blot, immunofluorescence, and RT-PCR.
Results:
The RMP expression in macrophages was markedly elevated in the kidneys of mice following folic acid administration or unilateral ureteral obstruction. Compared with wild-type mice subjected to folic acid stress or obstruction injury, macrophage-specific RMP knockout considerably aggravated collagen deposition and extracellular matrix protein production in injured kidneys. Moreover, loss of RMP in macrophages promoted proinflammatory cytokines release in the folic acid-injured or obstructed kidneys. Furthermore, macrophage RMP deficiency contributed to macrophages to myofibroblasts transition and increased myofibroblasts accumulation in folic acid or obstructive nephropathy. In cultured macrophages, the absence of RMP upregulated the expression of α-smooth muscle actin and enhanced the transition of macrophages to myofibroblasts.
Conclusions:
Our study reveals RMP as an important regulator of macrophage activation and kidney fibrosis progression. Hence, RMP may represent a promising therapeutic target for chronic kidney disease.
Insights
Macrophage RNA polymerase II subunit 5-mediating protein (RMP) is crucial in kidney fibrosis. Loss of RMP in macrophages worsens kidney inflammation and fibrosis, suggesting RMP as a therapeutic target for chronic kidney disease.
Area of Science:
- Nephrology
- Immunology
- Molecular Biology
Background:
- Chronic kidney disease involves kidney inflammation and fibrosis, with macrophages playing a key role.
- The precise molecular mechanisms of macrophage activation in kidney disease are not fully understood.
- This study investigates the role of macrophage RNA polymerase II subunit 5-mediating protein (RMP) in kidney inflammation and fibrosis.
Purpose of the Study:
- To examine the function of macrophage RNA polymerase II subunit 5-mediating protein (RMP) in the context of kidney inflammation and fibrosis.
- To elucidate the molecular mechanisms by which RMP influences macrophage activation and subsequent kidney damage.
Main Methods:
- Established mouse models of kidney fibrosis using folic acid administration and unilateral ureteral obstruction.
- Utilized macrophage-specific RMP knockout mice and wild-type controls for injury models.
- Assessed kidney collagen deposition, extracellular matrix protein expression, macrophage-to-myofibroblast transition, and inflammatory cytokines via histological staining, Western blot, immunofluorescence, and RT-PCR.
Main Results:
- Macrophage RMP expression increased in fibrotic kidneys.
- RMP deficiency in macrophages exacerbated collagen deposition and extracellular matrix production in injured kidneys.
- Loss of RMP promoted pro-inflammatory cytokine release and enhanced macrophage-to-myofibroblast transition, worsening kidney fibrosis.
Conclusions:
- Macrophage RNA polymerase II subunit 5-mediating protein (RMP) is a significant regulator of macrophage activation and kidney fibrosis progression.
- RMP presents a potential therapeutic target for managing chronic kidney disease and related fibrotic conditions.
