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Shenqi detoxification granule combined with P311 inhibits epithelial-mesenchymal transition in renal fibrosis via TGF-β1-Smad-ILK pathway.
Biosci Trends. 2017; 11(6):640-650.BT

Abstract

Shenqi detoxification granule (SDG), a traditional Chinese herbal formula, has been shown to have nephroprotective and anti-fibrotic activities in patients with chronic kidney disease (CKD). However, its mechanisms in renal fibrosis and the progression of CKD remain largely unknown. P311, a highly conserved 8-kDa intracellular protein, plays a key role in renal fibrosis by regulating epithelial-mesenchymal transition (EMT). Previously, we found P311 might be involved in the pathogenesis of renal fibrosis by inhibiting EMT via the TGF-β1-Smad-ILK pathway. We also found SDG combined with P311 could ameliorate renal fibrosis by regulating the expression of EMT markers. Here we further examined the effect and mechanism of SDG combined with P311 on TGF-β1-mediated EMT in a rat model of unilateral ureteral occlusion (UUO) renal fibrosis. After establishment of the UUO model successfully, the rats were gavaged with SDG daily and/or injected with recombinant adenovirus p311 (also called Ad-P311) through the tail vein each week for 4 weeks. Serum creatinine (Cr), blood urea nitrogen (BUN) and albumin (ALB) levels were tested to observe renal function, and hematoxylin eosin (HE) and Masson staining were performed to observe kidney histopathology. Furthermore, the expression of EMT markers (E-cadherin and α-smooth muscle actin (α-SMA)) and EMT-related molecules TGF-β1, pSmad2/3, Smad7 and ILK were observed using immunohistochemical staining and Western blot analysis. Treatment with SDG and P311 improved renal function and histopathological abnormalities, as well as reversing the changes of EMT markers and EMT-related molecules, which indicated SDG combined with P311 could attenuate renal fibrosis in UUO rats, and the underlying mechanism might involve TGF-β1-mediated EMT and the TGF-β1-Smad-ILK signaling pathway. Therefore, SDG might be a novel alternative therapy for treating renal fibrosis and delaying the progression of CKD. Furthermore, SDG combined with P311 might have a synergistic effect on attenuating renal fibrosis.

Authors+Show Affiliations

Department of Traditional Chinese Medicine, Shandong Provincial Hospital affiliated to Shandong University.Department of Nephrology, Shandong Provincial Hospital affiliated to Shandong University.Department of Traditional Chinese Medicine, Shandong Provincial Hospital affiliated to Shandong University.Department of Traditional Chinese Medicine, Shandong Provincial Hospital affiliated to Shandong University.Department of Traditional Chinese Medicine, Shandong Provincial Hospital affiliated to Shandong University.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

29311449

Citation

Cai, Pingping, et al. "Shenqi Detoxification Granule Combined With P311 Inhibits Epithelial-mesenchymal Transition in Renal Fibrosis Via TGF-β1-Smad-ILK Pathway." Bioscience Trends, vol. 11, no. 6, 2017, pp. 640-650.
Cai P, Liu X, Xu Y, et al. Shenqi detoxification granule combined with P311 inhibits epithelial-mesenchymal transition in renal fibrosis via TGF-β1-Smad-ILK pathway. Biosci Trends. 2017;11(6):640-650.
Cai, P., Liu, X., Xu, Y., Qi, F., & Si, G. (2017). Shenqi detoxification granule combined with P311 inhibits epithelial-mesenchymal transition in renal fibrosis via TGF-β1-Smad-ILK pathway. Bioscience Trends, 11(6), 640-650. https://doi.org/10.5582/bst.2017.01311
Cai P, et al. Shenqi Detoxification Granule Combined With P311 Inhibits Epithelial-mesenchymal Transition in Renal Fibrosis Via TGF-β1-Smad-ILK Pathway. Biosci Trends. 2017;11(6):640-650. PubMed PMID: 29311449.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Shenqi detoxification granule combined with P311 inhibits epithelial-mesenchymal transition in renal fibrosis via TGF-β1-Smad-ILK pathway. AU - Cai,Pingping, AU - Liu,Xiang, AU - Xu,Yuan, AU - Qi,Fanghua, AU - Si,Guomin, PY - 2018/1/10/entrez PY - 2018/1/10/pubmed PY - 2018/8/7/medline KW - P311 KW - Shenqi detoxification granule (SDG) KW - TGF-β1-Smad-ILK pathway KW - epithelial-mesenchymal transition (EMT) KW - renal fibrosis SP - 640 EP - 650 JF - Bioscience trends JO - Biosci Trends VL - 11 IS - 6 N2 - Shenqi detoxification granule (SDG), a traditional Chinese herbal formula, has been shown to have nephroprotective and anti-fibrotic activities in patients with chronic kidney disease (CKD). However, its mechanisms in renal fibrosis and the progression of CKD remain largely unknown. P311, a highly conserved 8-kDa intracellular protein, plays a key role in renal fibrosis by regulating epithelial-mesenchymal transition (EMT). Previously, we found P311 might be involved in the pathogenesis of renal fibrosis by inhibiting EMT via the TGF-β1-Smad-ILK pathway. We also found SDG combined with P311 could ameliorate renal fibrosis by regulating the expression of EMT markers. Here we further examined the effect and mechanism of SDG combined with P311 on TGF-β1-mediated EMT in a rat model of unilateral ureteral occlusion (UUO) renal fibrosis. After establishment of the UUO model successfully, the rats were gavaged with SDG daily and/or injected with recombinant adenovirus p311 (also called Ad-P311) through the tail vein each week for 4 weeks. Serum creatinine (Cr), blood urea nitrogen (BUN) and albumin (ALB) levels were tested to observe renal function, and hematoxylin eosin (HE) and Masson staining were performed to observe kidney histopathology. Furthermore, the expression of EMT markers (E-cadherin and α-smooth muscle actin (α-SMA)) and EMT-related molecules TGF-β1, pSmad2/3, Smad7 and ILK were observed using immunohistochemical staining and Western blot analysis. Treatment with SDG and P311 improved renal function and histopathological abnormalities, as well as reversing the changes of EMT markers and EMT-related molecules, which indicated SDG combined with P311 could attenuate renal fibrosis in UUO rats, and the underlying mechanism might involve TGF-β1-mediated EMT and the TGF-β1-Smad-ILK signaling pathway. Therefore, SDG might be a novel alternative therapy for treating renal fibrosis and delaying the progression of CKD. Furthermore, SDG combined with P311 might have a synergistic effect on attenuating renal fibrosis. SN - 1881-7823 UR - https://www.unboundmedicine.com/medline/citation/29311449/Shenqi_detoxification_granule_combined_with_P311_inhibits_epithelial_mesenchymal_transition_in_renal_fibrosis_via_TGF_β1_Smad_ILK_pathway_ L2 - https://dx.doi.org/10.5582/bst.2017.01311 DB - PRIME DP - Unbound Medicine ER -