Kaempferol Protects Renal Fibrosis through Activating the BMP-7-Smad1/5 Signaling Pathway

Abstract

Renal interstitial fibrosis (RIF) is a common pathological characteristic associated with end-stage renal disease. However, treatment strategies for RIF are still very limited. In this study, we reported that kaempferol, a classic flavonoid, exhibited strong and widely inhibitory effect on the expression of fibrosis related genes in transforming growth factor beta 1 (TGF-β1) treated NRK-52E cells. Further studies revealed that kaempferol inhibited TGF-β1 induced epithelial-mesenchymal transition (EMT) process of NRK-52E cells and improved renal function deterioration and RIF in unilateral ureteral obstruction (UUO) rats. After exploring the underlying mechanisms, we found that kaempferol was able to activate the BMP-7-Smad1/5 pathway, rather than the TGF-β1-Smad2/3 pathway. To further validate these results, DMH1 and BMP-7 knockdown were utilized at the cellular level and the results showed that both methods were able to antagonize the effects of kaempferol on the EMT process of NRK-52E cells induced by TGF-β1. In UUO rats, inhibition of BMP-7 signaling by DMH1 also reversed the effects of kaempferol on renal function decline and RIF. Taken together, our findings demonstrated that kaempferol could be a good candidate for renal fibrosis treatment.

Concentrated small extracellular vesicles from menstrual blood-derived stromal cells improve intrauterine adhesion, a pre-clinical study in a rat model

“…[48][49][50] In pulmonary and renal fibrosis, BMP7 facilitates scar repair by regulating SMAD1/5. 51,52 In this study, we confirmed that the protein expression of BMP7 and phosphorylation of SMAD1/5/ 8 were significantly increased after both MenSCs and MenSCs-sEVs transplantation. Guo et al also indicated decreased expression of BMP7 and SMAD1/5 in the uterus of the IUA rat model, suggesting that BMP7 may be a potential target for IUA treatment.…”

Ginaton injection alleviates cisplatin‑induced renal interstitial fibrosis in rats via inhibition of apoptosis through regulation of the p38MAPK/TGF‑β1 and p38MAPK/HIF‑1α pathways

“…Although SB functions in a similar manner to GBE, GBE was significantly more effective than SB in reducing p-P38 MAPK, TGF-β1 and HIF-1α protein expression levels, as well as renal apoptosis, injury and fibrosis. This may be due to the fact that GBE contains multiple active ingredients (55), and several of these may exhibit anti-fibrotic effects via different pathways, including quercetin and kaempferol (56,57). Kaempferoll exhibits an inhibitory effect on TGF-β1-induced fibrosis related genes in renal tubular epithelial cells, and improves renal function in rats (58).…”

Features of Cytokine Storm Identified by Distinguishing Clinical Manifestations in COVID-19

“…Some traditional Chinese drugs, such as Suctellaria baicalensis and Utrica dioica ( 24 ), as well as ginseng, have an inhibitory effect on TGF-β activity and can be used to alleviated symptoms of COVID-19 ( 25 ). Kaempferol, which can inhibit the secretion of mucus from goblet cells, is beneficial for the prevention and treatment of mucus hypersecretion of the lungs ( 26 , 27 ). Diterpene phenol extract of Rosmarinus officinalis has been reported to inhibit TGF-β in rats ( 28 ).…”