Tissue & cell · 2026
Iron-quercetin complex ameliorates chronic kidney disease via inhibiting the renal TGF-β1/Smad3/Egr1 axis-mediated kidney injury and fibrosis.
СтатьяНазвание и аннотация: Перевод в очереди
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Li Jianchun, Zhang Luna, Li Qianqian, Zou Yuanxia, Ni Yufang, Kantapan Jiraporn, Dechsupa Nathupakorn, Wang Li
Аннотация
BACKGROUND: Chronic kidney disease (CKD) remains a significant global health burden due to the lack of effective interventions. Here, we evaluated whether the metal-flavonoid compound, Iron-Quercetin complex (IronQ) can ameliorate CKD and examine its effect on the TGF-β1/Smad3/Egr1 signaling cascade.
METHODS: To assess the IronQ's therapeutic efficacy in renal fibrosis, two well-recognized in vivo models were employed: the unilateral ureteral obstruction (UUO) model and the adenine (Ade)-elicited renal fibrosis systems. The efficacy of IronQ was assessed through comprehensive analyses of renal injury and histopathological changes. In addition, an in vitro system of TGF-β1-induced profibrotic response was developed using renal fibroblasts (NRK-49F) and renal tubular cells (TCMK1) to dissect the cellular signaling. Furthermore, to elucidate the potential mechanisms by which IronQ ameliorates renal fibrosis, a proteomic screen was conducted to delineate the changes in protein expression after IronQ intervention.
RESULTS: IronQ significantly improved biochemical parameters of kidney injury, evidenced by a marked decrease in serum creatinine and blood urea nitrogen (BUN) levels. Consistently, IronQ treatment attenuated renal fibrosis, which was evidenced by a decreased expression of extracellular matrix (ECM) markers, including α-SMA, FN, and Col1a1, as evidenced by immunohistochemistry, Western blot, and qRT-PCR analyses. In agreement with the in vivo findings, IronQ intervention also significantly reduced the fibrotic response in both NRK-49F and TCMK-1 cell lines. Proteomic analysis further demonstrated that IronQ specifically downregulated the TGF-β1-stimulated upregulation of Egr1. Subsequent validation confirmed that the IronQ intervention significantly suppressed Egr1 expression and inhibited the phosphorylation of Smad3. Importantly, co-immunoprecipitation results revealed that IronQ intervention directly inhibited the physical interaction between Egr1 and Smad3.
CONCLUSION: Our research demonstrates that IronQ is a promising therapeutic candidate for CKD, offering a novel strategy to combat renal fibrosis via targeting the TGF-β1/Smad3/Egr1 cascade.
METHODS: To assess the IronQ's therapeutic efficacy in renal fibrosis, two well-recognized in vivo models were employed: the unilateral ureteral obstruction (UUO) model and the adenine (Ade)-elicited renal fibrosis systems. The efficacy of IronQ was assessed through comprehensive analyses of renal injury and histopathological changes. In addition, an in vitro system of TGF-β1-induced profibrotic response was developed using renal fibroblasts (NRK-49F) and renal tubular cells (TCMK1) to dissect the cellular signaling. Furthermore, to elucidate the potential mechanisms by which IronQ ameliorates renal fibrosis, a proteomic screen was conducted to delineate the changes in protein expression after IronQ intervention.
RESULTS: IronQ significantly improved biochemical parameters of kidney injury, evidenced by a marked decrease in serum creatinine and blood urea nitrogen (BUN) levels. Consistently, IronQ treatment attenuated renal fibrosis, which was evidenced by a decreased expression of extracellular matrix (ECM) markers, including α-SMA, FN, and Col1a1, as evidenced by immunohistochemistry, Western blot, and qRT-PCR analyses. In agreement with the in vivo findings, IronQ intervention also significantly reduced the fibrotic response in both NRK-49F and TCMK-1 cell lines. Proteomic analysis further demonstrated that IronQ specifically downregulated the TGF-β1-stimulated upregulation of Egr1. Subsequent validation confirmed that the IronQ intervention significantly suppressed Egr1 expression and inhibited the phosphorylation of Smad3. Importantly, co-immunoprecipitation results revealed that IronQ intervention directly inhibited the physical interaction between Egr1 and Smad3.
CONCLUSION: Our research demonstrates that IronQ is a promising therapeutic candidate for CKD, offering a novel strategy to combat renal fibrosis via targeting the TGF-β1/Smad3/Egr1 cascade.