Anti‑fibrotic effect of Sedum sarmentosum Bunge extract in kidneys via the hedgehog signaling pathway Corrigendum in /10.3892/mmr.2022.12658

Bai,Yongheng; Wu,Cunzao; Hong,Weilong; Zhang,Xing; Liu,Leping; Chen,Bicheng

doi:10.3892/mmr.2017.6628

Anti‑fibrotic effect of Sedum sarmentosum Bunge extract in kidneys via the hedgehog signaling pathway

Corrigendum in: /10.3892/mmr.2022.12658

Authors:
- Yongheng Bai
- Cunzao Wu
- Weilong Hong
- Xing Zhang
- Leping Liu
- Bicheng Chen
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Affiliations: Key Laboratory of Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, P.R. China, Department of Transplantation, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, P.R. China
Published online on: May 25, 2017 https://doi.org/10.3892/mmr.2017.6628
Pages: 737-745
Copyright: © Bai et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Sedum sarmentosum Bunge (SSBE) is a perennial plant widely distributed in Asian countries, and its extract is traditionally used for the treatment of certain inflammatory diseases. Our previous studies demonstrated that SSBE has marked renal anti‑fibrotic effects. However, the underlying molecular mechanisms remain to be fully elucidated. The present study identified that SSBE exerts its inhibitory effect on the myofibroblast phenotype and renal fibrosis via the hedgehog signaling pathway in vivo and in vitro. In rats with unilateral ureteral obstruction (UUO), SSBE administration reduced kidney injury and alleviated interstitial fibrosis by decreasing the levels of transforming growth factor (TGF)‑β1 and its receptor, and inhibiting excessive accumulation of extracellular matrix (ECM) components, including type I and III collagens. In addition, SSBE suppressed the expression of proliferating cell nuclear antigen, and this anti‑proliferative activity was associated with downregulation of hedgehog signaling activity in SSBE‑treated UUO kidneys. In cultured renal tubular epithelial cells (RTECs), recombinant TGF‑β1 activated hedgehog signaling, and resulted in induction of the myofibroblast phenotype. SSBE treatment inhibited the activation of hedgehog signaling and partially reversed the fibrotic phenotype in TGF‑β1‑treated RTECs. Similarly, aristolochic acid‑mediated upregulated activity of hedgehog signaling was reduced by SSBE treatment, and thereby led to the abolishment of excessive ECM accumulation. Therefore, these findings suggested that SSBE attenuates the myofibroblast phenotype and renal fibrosis via suppressing the hedgehog signaling pathway, and may facilitate the development of treatments for kidney fibrosis.

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1	Declèves AE and Sharma K: Novel targets of antifibrotic and anti-inflammatory treatment in CKD. Nat Rev Nephrol. 10:257–267. 2014. View Article : Google Scholar : PubMed/NCBI
2	Meran S and Steadman R: Fibroblasts and myofibroblasts in renal fibrosis. Int J Exp Pathol. 92:158–167. 2011. View Article : Google Scholar : PubMed/NCBI
3	Ding H, Zhou D, Hao S, Zhou L, He W, Nie J, Hou FF and Liu Y: Sonic hedgehog signaling mediates epithelial-mesenchymal communication and promotes renal fibrosis. J Am Soc Nephrol. 23:801–813. 2012. View Article : Google Scholar : PubMed/NCBI
4	Fabian SL, Penchev RR, St-Jacques B, Rao AN, Sipilä P, West KA, McMahon AP and Humphreys BD: Hedgehog-Gli pathway activation during kidney fibrosis. Am J Pathol. 180:1441–1453. 2012. View Article : Google Scholar : PubMed/NCBI
5	Gill PS and Rosenblum ND: Control of murine kidney development by sonic hedgehog and its GLI effectors. Cell Cycle. 5:1426–1430. 2006. View Article : Google Scholar : PubMed/NCBI
6	Choi SS, Omenetti A, Witek RP, Moylan CA, Syn WK, Jung Y, Yang L, Sudan DL, Sicklick JK, Michelotti GA, et al: Hedgehog pathway activation and epithelial-to-mesenchymal transitions during myofibroblastic transformation of rat hepatic cells in culture and cirrhosis. Am J Physiol Gastrointest Liver Physiol. 297:G1093–G1106. 2009. View Article : Google Scholar : PubMed/NCBI
7	Ninomiya K, Morikawa T, Zhang Y, Nakamura S, Matsuda H, Muraoka O and Yoshikawa M: Bioactive constituents from Chinese natural medicines. XXIII. Absolute structures of new megastigmane glycosides, sedumosides A(4), A(5), A(6), H, and I, and hepatoprotective megastigmanes from Sedum sarmentosum. Chem Pharm Bull (Tokyo). 55:1185–1191. 2007. View Article : Google Scholar : PubMed/NCBI
8	Morikawa T, Zhang Y, Nakamura S, Matsuda H, Muraoka O and Yoshikawa M: Bioactive constituents from Chinese natural medicines. XXII. Absolute structures of new megastigmane glycosides, sedumosides E₁, E₂, E₃, F₁, F₂ and G, from Sedum sarmentosum (Crassulaceae). Chem Pharm Bull (Tokyo). 55:435–441. 2007. View Article : Google Scholar : PubMed/NCBI
9	Oh H, Kang DG, Kwon JW, Kwon TO, Lee SY, Lee DB and Lee HS: Isolation of angiotensin converting enzyme (ACE) inhibitory flavonoids from Sedum sarmentosum. Biol Pharm Bull. 27:2035–2037. 2004. View Article : Google Scholar : PubMed/NCBI
10	Bai Y, Lu H, Hu L, Hong D, Ding L and Chen B: Effect of Sedum sarmentosum BUNGE extract on aristolochic acid-induced renal tubular epithelial cell injury. J Pharmacol Sci. 124:445–456. 2014. View Article : Google Scholar : PubMed/NCBI
11	Bai Y, Lu H, Zhang G, Wu C, Lin C, Liang Y and Chen B: Sedum sarmentosum Bunge extract exerts renal anti-fibrotic effects in vivo and in vitro. Life Sci. 105:22–30. 2014. View Article : Google Scholar : PubMed/NCBI
12	Cutcliffe C, Kersey D, Huang CC, Zeng Y, Walterhouse D and Perlman EJ: Renal Tumor Committee of the Children's Oncology Group: Clear cell sarcoma of the kidney: Up-regulation of neural markers with activation of the sonic hedgehog and Akt pathways. Clin Cancer Res. 11:7986–7994. 2005. View Article : Google Scholar : PubMed/NCBI
13	Yang L, Besschetnova TY, Brooks CR, Shah JV and Bonventre JV: Epithelial cell cycle arrest in G2/M mediates kidney fibrosis after injury. Nat Med. 16:535–543. 2010. View Article : Google Scholar : PubMed/NCBI
14	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(−Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI
15	Bhardwaj G, Murdoch B, Wu D, Baker DP, Williams KP, Chadwick K, Ling LE, Karanu FN and Bhatia M: Sonic hedgehog induces the proliferation of primitive human hematopoietic cells via BMP regulation. Nat Immunol. 2:172–180. 2001. View Article : Google Scholar : PubMed/NCBI
16	Omenetti A, Porrello A, Jung Y, Yang L, Popov Y, Choi SS, Witek RP, Alpini G, Venter J, Vandongen HM, et al: Hedgehog signaling regulates epithelial-mesenchymal transition during biliary fibrosis in rodents and humans. J Clin Invest. 118:3331–3342. 2008.PubMed/NCBI
17	Lu H, Chen B, Hong W, Liang Y and Bai Y: Transforming growth factor-β1 stimulates hedgehog signaling to promote epithelial-mesenchymal transition after kidney injury. FEBS J. 283:3771–3790. 2016. View Article : Google Scholar : PubMed/NCBI
18	Baudoux TE, Pozdzik AA, Arlt VM, De Prez EG, Antoine MH, Quellard N, Goujon JM and Nortier JL: Probenecid prevents acute tubular necrosis in a mouse model of aristolochic acid nephropathy. Kidney Int. 82:1105–1113. 2012. View Article : Google Scholar : PubMed/NCBI
19	Liu Y: Epithelial to mesenchymal transition in renal fibrogenesis: Pathologic significance, molecular mechanism, and therapeutic intervention. J Am Soc Nephrol. 15:1–12. 2004. View Article : Google Scholar : PubMed/NCBI
20	Humphreys BD, Valerius MT, Kobayashi A, Mugford JW, Soeung S, Duffield JS, McMahon AP and Bonventre JV: Intrinsic epithelial cells repair the kidney after injury. Cell Stem Cell. 2:284–291. 2008. View Article : Google Scholar : PubMed/NCBI
21	Liu Y: New insights into epithelial-mesenchymal transition in kidney fibrosis. J Am Soc Nephrol. 21:212–222. 2010. View Article : Google Scholar : PubMed/NCBI
22	di Magliano Pasca M and Hebrok M: Hedgehog signalling in cancer formation and maintenance. Nat Rev Cancer. 3:903–911. 2003. View Article : Google Scholar : PubMed/NCBI
23	Thayer SP, di Magliano MP, Heiser PW, Nielsen CM, Roberts DJ, Lauwers GY, Qi YP, Gysin S, Fernández-del Castillo C, Yajnik V, et al: Hedgehog is an early and late mediator of pancreatic cancer tumorigenesis. Nature. 425:851–856. 2003. View Article : Google Scholar : PubMed/NCBI
24	Hooper JE and Scott MP: Communicating with hedgehogs. Nat Rev Mol Cell Biol. 6:306–317. 2005. View Article : Google Scholar : PubMed/NCBI
25	Huang L, Walter V, Hayes DN and Onaitis M: Hedgehog-GLI signaling inhibition suppresses tumor growth in squamous lung cancer. Clin Cancer Res. 20:1566–1575. 2014. View Article : Google Scholar : PubMed/NCBI
26	Jung HJ, Kang HJ, Song YS, Park EH, Kim YM and Lim CJ: Anti-inflammatory, anti-angiogenic and anti-nociceptive activities of Sedum sarmentosum extract. J Ethnopharmacol. 116:138–143. 2008. View Article : Google Scholar : PubMed/NCBI
27	Johari J, Kianmehr A, Mustafa MR, Abubakar S and Zandi K: Antiviral activity of baicalein and quercetin against the Japanese encephalitis virus. Int J Mol Sci. 13:16785–16795. 2012. View Article : Google Scholar : PubMed/NCBI
28	Huang D, Zhang W, Huang D and Wu J: Antitumor activity of the aqueous extract from Sedum sarmentosum Bunge in vitro. Cancer Biother Radiopharm. 25:81–88. 2010. View Article : Google Scholar : PubMed/NCBI
29	Ge X, Wu Z, Wu Q, Yang F, Yang C and Yao X: Study of the effect and mechanism of Sedum sarmentosum Bunge on TNBS-induced colitis in rats. Chin J Integr Trad West Med Dig. 15:391–394. 2007.
30	Dong W, Cui J, Tian X, He L, Wang Z, Zhang P and Zhang H: Aberrant sonic hedgehog signaling pathway and STAT3 activation in papillary thyroid cancer. Int J Clin Exp Med. 7:1786–1793. 2014.PubMed/NCBI
31	Yang Q, Shen SS, Zhou S, Ni J, Chen D, Wang G and Li Y: STAT3 activation and aberrant ligand-dependent sonic hedgehog signaling in human pulmonary adenocarcinoma. Exp Mol Pathol. 93:227–236. 2012. View Article : Google Scholar : PubMed/NCBI
32	Maitah MY, Ali S, Ahmad A, Gadgeel S and Sarkar FH: Up-regulation of sonic hedgehog contributes to TGF-β1-induced epithelial to mesenchymal transition in NSCLC cells. PLoS One. 6:e160682011. View Article : Google Scholar : PubMed/NCBI