EUROPEAN JOURNAL OF
PHARMACEUTICAL AND MEDICAL RESEARCH

An International Peer Reviewed Journal for Pharmaceutical, Medical & Biological Sciences

An Official Publication of Society for Advance Healthcare Research (Reg. No. : 01/01/01/31674/16)

European Journal of Pharmaceutical and Medical Research (EJPMR) has indexed with various reputed international bodies like : Google Scholar , Indian Science Publications , InfoBase Index (In Process) , SOCOLAR, China , Research Bible, Fuchu, Tokyo. JAPAN , International Society for Research activity (ISRA) , Scientific Indexing Services (SIS) , Polish Scholarly Bibliography , Global Impact Factor (GIF) (Under Process) , Universal Impact Factor , International Scientific Indexing (ISI), UAE  , Index Copernicus , CAS (A Division of American Chemical Society) USA (Under Process) , Directory of Open Access Journal (DOAJ, Sweden, in process) , UDLedge Science Citation Index , CiteFactor , Directory Of Research Journal Indexing (DRJI) , Indian citation Index (ICI) , Journal Index (JI, Under Process) , Directory of abstract indexing for Journals (DAIJ) , Open Access Journals (Under Process) , Impact Factor Services For International Journals (IFSIJ) , Cosmos Impact Factor , Jour Informatics (Under Process) , Eurasian Scientific Journal Index (ESJI) , International Innovative Journal Impact Factor (IIJIF) , Science Library Index, Dubai, United Arab Emirates , Pubmed Database [NLM ID: 101669306] (Under Process) , 

 ISSN 2394- 3211

Impact Factor: 4.161

 ICV - 79.57

Abstract

THE MTOR INHIBITOR RAPAMYCIN INDUCES CTGF AND TIMP-1 EXPRESSION IN RAT KIDNEY: IMPLICATION OF TGF-?/SMAD SIGNALING CASCADE

Dr. Amany Balah* and Omnia Ezzate

ABSTRACT

The mTOR-inhibitor rapamycin is a potent drug used as immunosuppressive agent. It is usually used either alone or in combination with calcineurin inhibitors. Despite its beneficial role in organ transplantation rapamycin in some cases can promote fibrosis in the kidney. In cultured mesangial cells, rapamycin has been shown to activate TGF-/Smad signaling pathway in reactive oxygen species (ROS)-dependent manner. The present work was designed to test whether rapamycin-induced TGF-/Smad signaling pathway and subsequent profibrotic gene expression observed in cultured mesangial cells would also occur in vivo. The present work demonstrates that treatment of animals with rapamycin causes an increase in the expression of the profibrotic genes connective tissue growth factor (CTGF) and tissue inhibitor of metalloproteinase-1 (TIMP-1) on mRNA and protein levels in dose-dependent manner. Furthermore, it was found that rapamycin has the ability to activate TGF-/Smad signaling pathway in rat kidney as demonstrated by an increase in plasma TGF- level and subsequent Smad phosphorylation. Moreover, it was found that administration of the antioxidant N-acetyl cysteine (NAC) along with rapamycin significantly reduced plasma TGF-level and Smad-2 phosphorylation. Most interestingly, the expression of CTGF and TIMP-1 induced by rapamycin was highly reduced in the presence of either NAC or a neutralizing TGF- antibody on mRNA and protein levels indicating that ROS and subsequent TGF- activation are involved in CTGF and TIMP-1 expression induced by rapamycin. Finally, the present study demonstrates that rapamycin has the ability to induce CTGF and TIMP-1 expression in ROS and TGF--dependent manner in rat kidney (in vivo).

Keywords: Rapamycin, CTGF, TIMP-1, TGF-?, rat kidney.


[Full Text Article]

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Google Scholar Indian Science Publications InfoBase Index (In Process) SOCOLAR, China Research Bible, Fuchu, Tokyo. JAPAN International Society for Research activity (ISRA) Scientific Indexing Services (SIS) Polish Scholarly Bibliography Global Impact Factor (GIF) (Under Process) Universal Impact Factor International Scientific Indexing (ISI), UAE Index Copernicus CAS (A Division of American Chemical Society) USA (Under Process) Directory of Open Access Journal (DOAJ, Sweden, in process) UDLedge Science Citation Index CiteFactor Directory Of Research Journal Indexing (DRJI) Indian citation Index (ICI) Journal Index (JI, Under Process) Directory of abstract indexing for Journals (DAIJ) Open Access Journals (Under Process) Impact Factor Services For International Journals (IFSIJ) Cosmos Impact Factor Jour Informatics (Under Process) Eurasian Scientific Journal Index (ESJI) International Innovative Journal Impact Factor (IIJIF) Science Library Index, Dubai, United Arab Emirates Pubmed Database [NLM ID: 101669306] (Under Process)