Saikosaponin D Inhibits Peritoneal Fibrosis in Rats With Renal Failure by Regulation of TGFβ1/ BMP7 / Gremlin1/ Smad Pathway.

Saikosaponin D Inhibits Peritoneal Fibrosis in Rats With Renal Failure by Regulation of TGFβ1/ BMP7 / Gremlin1/ Smad Pathway.
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DOI:
10.3389/fphar.2021.628671
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发表时间:
2021
影响因子:
5.6
通讯作者:
Hongtao Y
Hongtao Y
中科院分区:
医学2区
文献类型:
--
作者:
Ruiqi L;Ming P;Qihang S;Yangyang L;Junli C;Wei L;Chao G;Xinyue L;Kang Y;Hongtao Y

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腹膜透析(PD)可以提高肾脏疾病患者的生活质量,延长生存期。然而,腹膜纤维化可经常发生并导致PD停药。因此,更好地了解如何抑制和减缓腹膜纤维化的进展是势在必行的。本研究旨在探讨柴胡单体柴胡皂苷d (Saikosaponin d, SSD)对腹膜纤维化的调控作用,以及tgf - β1/BMP7/Gremlin1通路串扰在这一过程中的作用。为此,我们采用大鼠5/6肾切除术和腹膜纤维化模型。将大鼠分为四组,即对照组(生理盐水);1模型组(给予透析液,M组);一个SSD组(透析液和SSD管理);阳性药物组(透析液加盐酸贝那普利M + a组)。组织学分析显示,所有组均发生腹膜纤维化。WB、ELISA和PCR分析结果显示,M组tgf - β1和Gremlin1表达水平显著高于C组,BMP7表达水平显著低于C组。tgf - β1、Gremlin1和BMP7水平在给予SSD组显著低于其他组。SSD组BMP7表达明显升高。此外,PCR检测的Smad1/5/8水平和WB检测的p-Smad1/5/8表达水平在SSD组也显著高于M组。两种重要的纤维化标志物vimentin和α-SMA的表达也显著降低。我们的研究表明tgf - β1/BMP7/Gremlin1/Smad通路在腹膜纤维化中的作用具有潜在的治疗意义。最后,我们的研究结果还表明,单体SSD可能能够通过调节tgf - β1/BMP7/Gremlin1/Smad途径逆转腹膜纤维化。
Peritoneal dialysis (PD) can improve the quality of life of patients with kidney disease and prolong survival. However, peritoneal fibrosis can often occur and lead to PD withdrawal. Therefore, it is imperative to better understand how to inhibit and slow down progression of peritoneal fibrosis. This study aimed to investigate the regulatory effect of Saikosaponin d (SSD), a monomer extracted from the plant Bupleurum, on peritoneal fibrosis and the contribution of TGFβ1/BMP7/Gremlin1 pathway cross-talk in this process. To this aim, we used a model 5/6 nephrectomy and peritoneal fibrosis in rats. Rats were divided into four groups, namely a control group (saline administration); a model group (dialysate administration; group M); a SSD group (dialysate and SSD administration); and a positive drug group (dialysate and Benazepril Hydrochloride administration; group M + A). Histological analysis indicated that peritoneal fibrosis occurred in all groups. WB, ELISA, and PCR essays suggested that TGFβ1 and Gremlin1 levels in group M were significantly higher than those in group C, whereas BMP7 expression was significantly lower. TGFβ1, Gremlin1 and BMP7 levels were significantly lower in the group where SSD was administered than in the other groups. The expression of BMP7 in SSD group was significantly increased. In addition, levels of Smad1/5/8 as assessed by PCR, and levels of p-Smad1/5/8 expression as assessed by WB were also significantly higher in the SSD group than in the M group. Expression of vimentin and α-SMA, two important markers of fibrosis, was also significantly decreased. Our study suggests a role for the TGFβ1/BMP7/Gremlin1/Smad pathway in peritoneal fibrosis with potential therapeutic implications. Finally, our results also suggest that the monomer SSD may be able to reverse peritoneal fibrosis via regulation of the TGFβ1/BMP7/Gremlin1/Smad pathway.
DOI: 10.1016/s0140-6736(14)61682-2
发表时间: 2015-01-10
期刊: LANCET
影响因子: 168.9
作者:
Naghavi, Mohsen;Wang, Haidong;Lozano, Rafael;Davis, Adrian;Liang, Xiaofeng;Zhou, Maigeng;Vollset, Stein Emil;Ozgoren, Ayse Abbasoglu;Abdalla, Safa;Abd-Allah, Foad;Aziz, Muna I. Abdel;Abera, Semaw Ferede;Aboyans, Victor;Abraham, Biju;Abraham, Jerry P.;Abuabara, Katrina E.;Abubakar, Ibrahim;Abu-Raddad, Laith J.;Abu-Rmeileh, Niveen M. E.;Achoki, Tom;Adelekan, Ademola;Ademi, Zanfi Na;Adofo, Koranteng;Adou, Arsene Kouablan;Adsuar, Jose C.;Arnlov, Johan;Agardh, Emilie Elisabet;Akena, Dickens;Al Khabouri, Mazin J.;Alasfoor, Deena;Albittar, Mohammed;Alegretti, Miguel Angel;Aleman, Alicia V.;Alemu, Zewdie Aderaw;Alfonso-Cristancho, Rafael;Alhabib, Samia;Ali, Mohammed K.;Ali, Raghib;Alla, Francois;Al Lami, Faris;Allebeck, Peter;AlMazroa, Mohammad A.;Salman, Rustam Al-Shahi;Alsharif, Ubai;Alvarez, Elena;Alviz-Guzman, Nelson;Amankwaa, Adansi A.;Amare, Azmeraw T.;Ameli, Omid;Amini, Hassan;Ammar, Walid;Anderson, H. Ross;Anderson, Benjamin O.;Antonio, Carl Abelardo T.;Anwari, Palwasha;Apfel, Henry;Cunningham, Solveig Argeseanu;Arsenijevic, Valentina S. Arsic;Al Artaman;Asad, Majed Masoud;Asghar, Rana J.;Assadi, Reza;Atkins, Lydia S.;Atkinson, Charles;Badawi, Alaa;Bahit, Maria C.;Bakfalouni, Talal;Balakrishnan, Kalpana;Balalla, Shivanthi;Banerjee, Amitava;Barber, Ryan M.;Barker-Collo, Suzanne L.;Barquera, Simon;Barregard, Lars;Barrero, Lope H.;Barrientos-Gutierrez, Tonatiuh;Basu, Arindam;Basu, Sanjay;Basulaiman, Mohammed Omar;Beardsley, Justin;Bedi, Neeraj;Beghi, Ettore;Bekele, Tolesa;Bell, Michelle L.;Benjet, Corina;Bennett, Derrick A.;Bensenor, Isabela M.;Benzian, Habib;Bertozzi-Villa, Amelia;Beyene, Tariku Jibat;Bhala, Neeraj;Bhalla, Ashish;Bhutta, Zulfiqar A.;Bikbov, Boris;Bin Abdulhak, Aref;Biryukov, Stan;Blore, Jed D.;Blyth, Fiona M.;Bohensky, Megan A.;Borges, Guilherme;Bose, Dipan;Boufous, Soufiane;Bourne, Rupert R.;Boyers, Lindsay N.;Brainin, Michael;Brauer, Michael;Brayne, Carol E. G.;Brazinova, Alexandra;Breitborde, Nicholas;Brenner, Hermann;Briggs, Adam D. M.;Brown, Jonathan C.;Brugha, Traolach S.;Buckle, Geoffrey C.;Bui, Linh Ngoc;Bukhman, Gene;Burch, Michael;Nonato, Ismael Ricardo Campos;Carabin, Helesne;Cardenas, Rosario;Carapetis, Jonathan;Carpenter, David O.;Caso, Valeria;Castaneda-Orjuela, Carlos A.;Castro, Ruben Estanislao;Catala-Lopez, Ferrn;Cavalleri, Fiorella;Chang, Jung-Chen;Charlson, Fiona C.;Che, Xuan;Chen, Honglei;Chen, Yingyao;Chen, Jian Sheng;Chen, Zhengming;Chiang, Peggy Pei-Chia;Chimed-Ochir, Odgerel;Chowdhury, Rajiv;Christensen, Hanne;Christophi, Costas A.;Chuang, Ting-Wu;Chugh, Sumeet S.;Cirillo, Massimo;Coates, Matthew M.;Coffeng, Luc Edgar;Coggeshall, Megan S.;Cohen, Aaron;Colistro, Valentina;Colquhoun, Samantha M.;Colomar, Mercedes;Cooper, Leslie Trumbull;Cooper, Cyrus;Coppola, Luis M.;Cortinovis, Monica;Courville, Karen;Cowie, Benjamin C.;Criqui, Michael H.;Crump, John A.;Cuevas-Nasu, Lucia;Leite, Iuri da Costa;Dabhadkar, Kaustubh C.;Dandona, Lalit;Dandona, Rakhi;Dansereau, Emily;Dargan, Paul I.;Dayama, Anand;De la Cruz-Gongora, Vanessa;de la Vega, Shelley F.;De Leo, Diego;Degenhardt, Louisa;del Pozo-Cruz, Borja;Dellavalle, Robert P.;Deribe, Kebede;Jarlais, Don C. Des;Dessalegn, Muluken;deVeber, Gabrielle A.;Dharmaratne, Samath D.;Dherani, Mukesh;Diaz-Ortega, Jose-Luis;Diaz-Torne, Cesar;Dicker, Daniel;Ding, Eric L.;Dokova, Klara;Dorsey, E. Ray;Driscoll, Tim R.;Duan, Leilei;Duber, Herbert C.;Durrani, Adnan M.;Ebel, Beth E.;Edmond, Karen M.;Ellenbogen, Richard G.;Elshrek, Yousef;Ermakov, Sergey Petrovich;Erskine, Holly E.;Eshrati, Babak;Esteghamati, Alireza;Estep, Kara;Fuerst, Thomas;Fahimi, Saman;Fahrion, Anna S.;Faraon, Emerito Jose A.;Farzadfar, Farshad;Fay, Derek F. J.;Feigl, Andrea B.;Feigin, Valery L.;Felicio, Manuela Mendonca;Fereshtehnejad, Seyed-Mohammad;Fernandes, Jefferson G.;Ferrari, Alize J.;Fleming, Thomas D.;Foigt, Nataliya;Foreman, Kyle;Forouzanfar, Mohammad H.;Fowkes, F. Gerry R.;Fra Paleo, Urbano;Franklin, Richard C.;Futran, Neal D.;Gaffikin, Lynne;Gambashidze, Ketevan;Gankpe, Fortune Gbetoho;Garcia-Guerra, Francisco Armando;Garcia, Ana Cristina;Geleijnse, Johanna M.;Gessner, Bradford D.;Gibney, Katherine B.;Gillum, Richard F.;Gilmour, Stuart;Abdelmageem, Ibrahim;Ginawi, Mohamed;Giroud, Maurice;Glaser, Elizabeth L.;Goenka, Shifalika;Dantes, Hector Gomez;Gona, Philimon;Gonzalez-Medina, Diego;Guinovart, Caterina;Gupta, Rahul;Gupta, Rajeev;Gosselin, Richard A.;Gotay, Carolyn C.;Goto, Atsushi;Gowda, Hube N.;Graetz, Nicholas;Greenwell, K. Fern;Gugnani, Harish Chander;Gunnell, David;Gutierrez, Reyna A.;Haagsma, Juanita;Hafezi-Nejad, Nima;Hagan, Holly;Hagstromer, Maria;Halasa, Yara A.;Hamadeh, Randah Ribhi;Hamavid, Hannah;Hammami, Mouhanad;Hancock, Jamie;Hankey, Graeme J.;Hansen, Gillian M.;Harb, Hilda L.;Harewood, Heather;Haro, Josep Maria;Havmoeller, Rasmus;Hay, Roderick J.;Hay, Simon I.;Hedayati, Mohammad T.;Pi, Ileana B. Heredia;Heuton, Kyle R.;Heydarpour, Pouria;Higashi, Hideki;Hijar, Martha;Hoek, Hans W.;Hoffman, Howard J.;Hornberger, John C.;Hosgood, H. 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B.;Leasher, Janet L.;Lee, Jong-Tae;Leigh, James;Leinsalu, Mall;Leung, Ricky;Levitz, Carly;Li, Bin;Li, Yichong;Li, Yongmei;Liddell, Chelsea;Lim, Stephen S.;de Lima, Graca Maria Ferreira;Lind, Maggie L.;Lipshultz, Steven E.;Liu, Shiwei;Liu, Yang;Lloyd, Belinda K.;Lofgren, Katherine T.;Logroscino, Giancarlo;London, Stephanie J.;Lortet-Tieulent, Joannie;Lotufo, Paulo A.;Lucas, Robyn M.;Lunevicius, Raimundas;Lyons, Ronan Anthony;Ma, Stefan;Machado, Vasco Manuel Pedro;MacIntyre, Michael F.;Mackay, Mark T.;MacLachlan, Jennifer H.;Magis-Rodriguez, Carlos;Mahdi, Abbas A.;Majdan, Marek;Malekzadeh, Reza;Mangalam, Srikanth;Mapoma, Christopher Chabila;Marape, Marape;Marcenes, Wagner;Margono, Christopher;Marks, Guy B.;Marzan, Melvin Barrientos;Masci, Joseph R.;Mashal, Mohammad Taufi Q.;Masiye, Felix;Mason-Jones, Amanda J.;Matzopolous, Richard;Mayosi, Bongani M.;Mazorodze, Tasara T.;McGrath, John J.;Mckay, Abigail C.;Mckee, Martin;McLain, Abigail;Meaney, Peter A.;Mehndiratta, Man Mohan;Mejia-Rodriguez, Fabiola;Melaku, Yohannes Adama;Meltzer, Michele;Memish, Ziad A.;Mendoza, Walter;Mensah, George A.;Meretoja, Atte;Mhimbira, Francis A.;Miller, Ted R.;Mills, Edward J.;Misganaw, Awoke;Mishra, Santosh K.;Mock, Charles N.;Moffitt, Terrie E.;Ibrahim, Norlinah Mohamed;Mohammad, Karzan Abdulmuhsin;Mokdad, Ali H.;Mola, Glen Liddell;Monasta, Lorenzo;Monis, Jonathan de la Cruz;Hernandez, Julio C. Montaez;Montico, Marcella;Montine, Thomas J.;Mooney, Meghan D.;Moore, Ami R.;Moradi-Lakeh, Maziar;Moran, Andrew E.;Mori, Rintaro;Moschandreas, Joanna;Moturi, Wilkister Nyaora;Moyer, Madeline L.;Mozaffarian, Dariush;Mueller, Ulrich O.;Mukaigawara, Mitsuru;Mullany, Erin C.;Murray, Joseph;Mustapha, Adetoun;Naghavi, Paria;Naheed, Aliya;Naidoo, Kovin S.;Naldi, Luigi;Nand, Devina;Nangia, Vinay;Narayan, K. M. Venkat;Nash, Denis;Nasher, Jamal;Nejjari, Chakib;Nelson, Robert G.;Neuhouser, Marian;Neupane, Sudan Prasad;Newcomb, Polly A.;Newman, Lori;Newton, Charles R.;Ng, Marie;Ngalesoni, Frida Namnyak;Nguyen, Grant;Nhung Thi Trang Nguyen;Nisar, Muhammad Imran;Nolte, Sandra;Norheim, Ole F.;Norman, Rosana E.;Norrving, Bo;Nyakarahuka, Luke;Odell, Shaun;O'Donnell, Martin;Ohkubo, Takayoshi;Ohno, Summer Lockett;Olusanya, Bolajoko O.;Omer, Saad B.;Opio, John Nelson;Orisakwe, Orish Ebere;Ortblad, Katrina F.;Ortiz, Alberto;Otayza, Maria Lourdes K.;Pain, Amanda W.;Pandian, Jeyaraj D.;Panelo, Carlo Irwin;Panniyammakal, Jeemon;Papachristou, Christina;Paternina Caicedo, Angel J.;Patten, Scott B.;Patton, George C.;Paul, Vinod K.;Pavlin, Boris;Pearce, Neil;Pellegrini, Carlos A.;Pereira, David M.;Peresson, Sophie C.;Perez-Padilla, Rogelio;Perez-Ruiz, Fernando P.;Perico, Norberto;Pervaiz, Aslam;Pesudovs, Konrad;Peterson, Carrie B.;Petzold, Max;Phillips, Bryan K.;Phillips, David E.;Phillips, Michael R.;Plass, Dietrich;Piel, Frederic Bernard;Poenaru, Dan;Polinder, Suzanne;Popova, Svetlana;Poulton, Richie G.;Pourmalek, Farshad;Prabhakaran, Dorairaj;Qato, Dima;Quezada, Amado D.;Quistberg, D. Alex;Rabito, Felicia;Rafay, Anwar;Rahimi, Kazem;Rahimi-Movaghar, Vafa;Rahman, Sajjad U. R.;Raju, Murugesan;Rakovac, Ivo;Rana, Saleem M.;Refaat, Amany;Remuzzi, Giuseppe;Ribeiro, Antonio L.;Ricci, Stefano;Riccio, Patricia M.;Richardson, Lee;Richardus, Jan Hendrik;Roberts, Bayard;Roberts, D. Allen;Robinson, Margaret;Roca, Anna;Rodriguez, Alina;Rojas-Rueda, David;Ronfani, Luca;Room, Robin;Roth, Gregory A.;Rothenbacher, Dietrich;Rothstein, David H.;Rowley, Jane Tf;Roy, Nobhojit;Ruhago, George M.;Rushton, Lesley;Sambandam, Sankar;Soreide, Kjetil;Saeedi, Mohammad Yahya;Saha, Sukanta;Sahathevan, Ramesh;Sahraian, Mohammad Ali;Sahle, Berhe Weldearegawi;Salomon, Joshua A.;Salvo, Deborah;Samonte, Genesis May J.;Sampson, Uchechukwu;Sanabria, Juan Ramon;Sandar, Logan;Santos, Itamar S.;Satpathy, Maheswar;Sawhney, Monika;Saylan, Mete;Scarborough, Peter;Schoettker, Ben;Schmidt, Juergen C.;Schneider, Ione J. C.;Schumacher, Austin E.;Schwebel, David C.;Scott, James G.;Sepanlou, Sadaf G.;Servan-Mori, Edson E.;Shackelford, Katya;Shaheen, Amira;Shahraz, Saeid;Shakh-Nazarova, Marina;Shangguan, Siyi;She, Jun;Sheikhbahaei, Sara;Shepard, Donald S.;Shibuya, Kenji;Shinohara, Yukito;Shishani, Kawkab;Shiue, Ivy;Shivakoti, Rupak;Shrime, Mark G.;Sigfusdottir, Inga Dora;Silberberg, Donald H.;Silva, Andrea P.;Simard, Edgar P.;Sindi, Shireen;Singh, Jasvinder A.;Singh, Lavanya;Sioson, Edgar;Skirbekk, Vegard;Sliwa, Karen;So, Samuel;Soljak, Michael;Soneji, Samir;Soshnikov, Sergey S.;Sposato, Luciano A.;Sreeramareddy, Chandrashekhar T.;Stanaway, Jeff Rey D.;Stathopoulou, Vasiliki Kalliopi;Steenland, Kyle;Stein, Claudia;Steiner, Caitlyn;Stevens, Antony;Stoeckl, Heidi;Straif, Kurt;Stroumpoulis, Konstantinos;Sturua, Lela;Sunguya, Bruno F.;Swaminathan, Soumya;Swaroop, Mamta;Sykes, Bryan L.;Tabb, Karen M.;Takahashi, Ken;Talongwa, Roberto Tchio;Tan, Feng;Tanne, David;Tanner, Marcel;Tavakkoli, Mohammad;Ao, Braden Te;Teixeira, Carolina Maria;Templin, Tara;Tenkorang, Eric Yeboah;Terkawi, Abdullah Sulieman;Thomas, Bernadette A.;Thorne-Lyman, Andrew L.;Thrift, Amanda G.;Thurston, George D.;Tillmann, Taavi;Tirschwell, David L.;Tleyjeh, Imad M.;Tonelli, Marcello;Topouzis, Fotis;Towbin, Jeffrey A.;Toyoshima, Hideaki;Traebert, Jefferson;Tran, Bach X.;Truelsen, Thomas;Trujillo, Ulises;Trillini, Matias;Dimbuene, Zacharie Tsala;Tsilimbaris, Miltiadis;Tuzcu, E. Murat;Ubeda, Clotilde;Uchendu, Uche S.;Ukwaja, Kingsley N.;Undurraga, Eduardo A.;Vallely, Andrew J.;van de Vijver, Steven;van Gool, Coen H.;Varakin, Yuri Y.;Vasankari, Tommi J.;Vasconcelos, Ana Maria Nogales;Vavilala, Monica S.;Venketasubramanian, N.;Vijayakumar, Lakshmi;Villalpando, Salvador;Violante, Francesco S.;Vlassov, Vasiliy Victorovich;Wagner, Gregory R.;Waller, Stephen G.;Wang, JianLi;Wang, Linhong;Wang, XiaoRong;Wang, Yanping;Warouw, Tati Suryati;Weichenthal, Scott;Weiderpass, Elisabete;Weintraub, Robert G.;Wenzhi, Wang;Werdecker, Andrea;Wessells, K. Ryan R.;Westerman, Ronny;Whiteford, Harvey A.;Wilkinson, James D.;Williams, Thomas Neil;Woldeyohannes, Solomon Meseret;Wolfe, Charles D. A.;Wolock, Timothy M.;Woolf, Anthony D.;Wong, John Q.;Wright, Jonathan L.;Wulf, Sarah;Wurtz, Brittany;Xu, Gelin;Yang, Yang C.;Yano, Yuichiro;Yatsuya, Hiroshi;Yip, Paul;Yonemoto, Naohiro;Yoon, Seok-Jun;Younis, Mustafa;Yu, Chuanhua;Jin, Kim Yun;Zaki, Maysaa El Sayed;Zamakhshary, Mohammed Fouad;Zeeb, Hajo;Zhang, Yong;Zhao, Yong;Zheng, Yingfeng;Zhu, Jun;Zhu, Shankuan;Zonies, David;Zou, Xiao Nong;Zunt, Joseph R.;Vos, Theo;Lopez, Alan D.;Murray, Christopher J. L.
通讯作者: Murray, Christopher J. L.
DOI: 10.1093/ndt/gfq032
发表时间: 2010-04-01
影响因子: 6.1
作者:
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通讯作者: Fraser, Donald J.
DOI: 10.1016/j.cbi.2019.01.005
发表时间: 2019-02-25
影响因子: 5.1
作者:
Cui, Li-Hua;Li, Cai-Xia;Zhang, Shu-Kun
通讯作者: Zhang, Shu-Kun
DOI: 10.1159/000346575
发表时间: 2012-01-01
影响因子: --
作者:
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通讯作者: Ruiz-Ortega, Marta
DOI: 10.1155/2014/802841
发表时间: 2014
影响因子: --
作者:
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通讯作者: Ruiz-Ortega M