Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026
Macrophage RNA polymerase II subunit 5-mediating protein deficiency exacerbates kidney inflammation and fibrosis.
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Nie Jiayi, Liu Benquan, Xiong Heng, Gao Ying, Li Shuiying, Chen Shuangquan, Yu Wenqiang, Liang Hua
Аннотация
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.
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.