Therapeutic Potential of Silymarin in Inhibiting the Fibroblast-to-Myofibroblast Transition in Renal Interstitial Fibroblasts
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Renal fibrosis (RF) is a prominent pathological feature of chronic kidney disease (CKD), characterized by excessive accumulation of extracellular matrix components, resulting in progressive renal function loss. The fibroblast-to-myofibroblast transition (FMT) plays a pivotal role in renal fibrosis pathogenesis, driving aberrant deposition of extracellular matrix proteins and disruption of tissue architecture. Targeting FMT has emerged as a promising strategy to combat renal fibrosis and preserve kidney function. Silymarin, a flavonoid extract derived from Silybum marianum seeds, has gained attention for its therapeutic potential, particularly in liver diseases, due to its potent antioxidant and anti-inflammatory properties. However, the precise mechanisms underlying its effects on FMT remain unclear. This study aimed to investigate the therapeutic potential of silymarin in inhibiting FMT in NRK-49F renal interstitial fibroblasts. Transforming growth factor-beta 1(TGF-β1) plays a crucial role in promoting FMT through the activation of intracellular signaling pathways and induction of key fibrotic markers, including alpha-smooth muscle actin (α-SMA) and vimentin. Silymarin demonstrated significant downregulation of FMT markers, including α-SMA and vimentin, in TGF-β1-stimulated NRK-49F cells. Our findings highlight silymarin as a promising therapeutic candidate for mitigating renal fibrosis and managing CKD.
Abstract
Renal fibrosis (RF) is a prominent pathological feature of chronic kidney disease (CKD), characterized by excessive accumulation of extracellular matrix components, resulting in progressive renal function loss. The fibroblast-to-myofibroblast transition (FMT) plays a pivotal role in renal fibrosis pathogenesis, driving aberrant deposition of extracellular matrix proteins and disruption of tissue architecture. Targeting FMT has emerged as a promising strategy to combat renal fibrosis and preserve kidney function. Silymarin, a flavonoid extract derived from Silybum marianum seeds, has gained attention for its therapeutic potential, particularly in liver diseases, due to its potent antioxidant and anti-inflammatory properties. However, the precise mechanisms underlying its effects on FMT remain unclear. This study aimed to investigate the therapeutic potential of silymarin in inhibiting FMT in NRK-49F renal interstitial fibroblasts. Transforming growth factor-beta 1(TGF-β1) plays a crucial role in promoting FMT through the activation of intracellular signaling pathways and induction of key fibrotic markers, including alpha-smooth muscle actin (α-SMA) and vimentin. Silymarin demonstrated significant downregulation of FMT markers, including α-SMA and vimentin, in TGF-β1-stimulated NRK-49F cells. Our findings highlight silymarin as a promising therapeutic candidate for mitigating renal fibrosis and managing CKD.
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