Academic Journal
Interaction of tacrolimus through hedgehog signaling pathway: An in vitro evaluation using rat hepatocytes
| العنوان: | Interaction of tacrolimus through hedgehog signaling pathway: An in vitro evaluation using rat hepatocytes |
|---|---|
| المؤلفون: | Fatima, N, Sheikh, N, Satoskar, AR, Jha, BK, Akhtar, T, Tayyeb, A, Ashfaq, I |
| المصدر: | Human & Experimental Toxicology ; volume 40, issue 11, page 1955-1961 ; ISSN 0960-3271 1477-0903 |
| بيانات النشر: | SAGE Publications |
| سنة النشر: | 2021 |
| الوصف: | Tacrolimus (TAC) is the drug of choice in immunosuppressive therapy for organ transplantation; however, adverse effects are still a major concern. The current study aims to decipher the short-term exposure of TAC on rat hepatocytes in relation to activation of hedgehog (HH) signaling pathway. Time dependent study was conducted using primary rat hepatocytes treated with TAC (36 µM) for 6, 12, 24 and 48 h. Western blot analysis was performed using cell lysate in order to analyze the regulation of HH pathway proteins including HHIP, SMO, PTCH, IHH, SHH, and GLI transcription factors. The study revealed change in protein expression of HH signaling molecules with activation of HH pathway, due to downregulation of HHIP, and enrichment of HH ligands with activation of SMO and GLI transcription factors. It is therefore, concluded that short term TAC exposure leads to upregulation of HH pathway in liver, which may initially act to repair the liver damage but can worsen the condition in case of prolonged immunosuppressive therapy. This insight could lead to understand association of off target effects of immunosuppressive drugs and occurrence of other liver diseases in transplant patients when it comes to long term immunosuppressive therapy. These findings also illuminate a novel direction that use of HH inhibitor might provide a therapeutic strategy for immune suppression related liver disorders. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| DOI: | 10.1177/09603271211017313 |
| الاتاحة: | https://doi.org/10.1177/09603271211017313 https://journals.sagepub.com/doi/pdf/10.1177/09603271211017313 https://journals.sagepub.com/doi/full-xml/10.1177/09603271211017313 |
| Rights: | https://journals.sagepub.com/page/policies/text-and-data-mining-license |
| رقم الانضمام: | edsbas.7F33C5BE |
| قاعدة البيانات: | BASE |
| ResultId |
1 |
|---|---|
| Header |
edsbas BASE edsbas.7F33C5BE 919 3 Academic Journal academicJournal 918.9462890625 |
| PLink |
https://search.ebscohost.com/login.aspx?direct=true&site=eds-live&scope=site&db=edsbas&AN=edsbas.7F33C5BE&custid=s6537998&authtype=sso |
| FullText |
Array
(
[Availability] => 0
)
Array ( [0] => Array ( [Url] => https://doi.org/10.1177/09603271211017313# [Name] => EDS - BASE [Category] => fullText [Text] => View record in BASE [MouseOverText] => View record in BASE ) ) |
| Items |
Array
(
[Name] => Title
[Label] => Title
[Group] => Ti
[Data] => Interaction of tacrolimus through hedgehog signaling pathway: An in vitro evaluation using rat hepatocytes
)
Array ( [Name] => Author [Label] => Authors [Group] => Au [Data] => <searchLink fieldCode="AR" term="%22Fatima%2C+N%22">Fatima, N</searchLink><br /><searchLink fieldCode="AR" term="%22Sheikh%2C+N%22">Sheikh, N</searchLink><br /><searchLink fieldCode="AR" term="%22Satoskar%2C+AR%22">Satoskar, AR</searchLink><br /><searchLink fieldCode="AR" term="%22Jha%2C+BK%22">Jha, BK</searchLink><br /><searchLink fieldCode="AR" term="%22Akhtar%2C+T%22">Akhtar, T</searchLink><br /><searchLink fieldCode="AR" term="%22Tayyeb%2C+A%22">Tayyeb, A</searchLink><br /><searchLink fieldCode="AR" term="%22Ashfaq%2C+I%22">Ashfaq, I</searchLink> ) Array ( [Name] => TitleSource [Label] => Source [Group] => Src [Data] => Human & Experimental Toxicology ; volume 40, issue 11, page 1955-1961 ; ISSN 0960-3271 1477-0903 ) Array ( [Name] => Publisher [Label] => Publisher Information [Group] => PubInfo [Data] => SAGE Publications ) Array ( [Name] => DatePubCY [Label] => Publication Year [Group] => Date [Data] => 2021 ) Array ( [Name] => Abstract [Label] => Description [Group] => Ab [Data] => Tacrolimus (TAC) is the drug of choice in immunosuppressive therapy for organ transplantation; however, adverse effects are still a major concern. The current study aims to decipher the short-term exposure of TAC on rat hepatocytes in relation to activation of hedgehog (HH) signaling pathway. Time dependent study was conducted using primary rat hepatocytes treated with TAC (36 µM) for 6, 12, 24 and 48 h. Western blot analysis was performed using cell lysate in order to analyze the regulation of HH pathway proteins including HHIP, SMO, PTCH, IHH, SHH, and GLI transcription factors. The study revealed change in protein expression of HH signaling molecules with activation of HH pathway, due to downregulation of HHIP, and enrichment of HH ligands with activation of SMO and GLI transcription factors. It is therefore, concluded that short term TAC exposure leads to upregulation of HH pathway in liver, which may initially act to repair the liver damage but can worsen the condition in case of prolonged immunosuppressive therapy. This insight could lead to understand association of off target effects of immunosuppressive drugs and occurrence of other liver diseases in transplant patients when it comes to long term immunosuppressive therapy. These findings also illuminate a novel direction that use of HH inhibitor might provide a therapeutic strategy for immune suppression related liver disorders. ) Array ( [Name] => TypeDocument [Label] => Document Type [Group] => TypDoc [Data] => article in journal/newspaper ) Array ( [Name] => Language [Label] => Language [Group] => Lang [Data] => English ) Array ( [Name] => DOI [Label] => DOI [Group] => ID [Data] => 10.1177/09603271211017313 ) Array ( [Name] => URL [Label] => Availability [Group] => URL [Data] => https://doi.org/10.1177/09603271211017313<br />https://journals.sagepub.com/doi/pdf/10.1177/09603271211017313<br />https://journals.sagepub.com/doi/full-xml/10.1177/09603271211017313 ) Array ( [Name] => Copyright [Label] => Rights [Group] => Cpyrght [Data] => https://journals.sagepub.com/page/policies/text-and-data-mining-license ) Array ( [Name] => AN [Label] => Accession Number [Group] => ID [Data] => edsbas.7F33C5BE ) |
| RecordInfo |
Array
(
[BibEntity] => Array
(
[Identifiers] => Array
(
[0] => Array
(
[Type] => doi
[Value] => 10.1177/09603271211017313
)
)
[Languages] => Array
(
[0] => Array
(
[Text] => English
)
)
[Titles] => Array
(
[0] => Array
(
[TitleFull] => Interaction of tacrolimus through hedgehog signaling pathway: An in vitro evaluation using rat hepatocytes
[Type] => main
)
)
)
[BibRelationships] => Array
(
[HasContributorRelationships] => Array
(
[0] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => Fatima, N
)
)
)
[1] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => Sheikh, N
)
)
)
[2] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => Satoskar, AR
)
)
)
[3] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => Jha, BK
)
)
)
[4] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => Akhtar, T
)
)
)
[5] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => Tayyeb, A
)
)
)
[6] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => Ashfaq, I
)
)
)
)
[IsPartOfRelationships] => Array
(
[0] => Array
(
[BibEntity] => Array
(
[Dates] => Array
(
[0] => Array
(
[D] => 01
[M] => 01
[Type] => published
[Y] => 2021
)
)
[Identifiers] => Array
(
[0] => Array
(
[Type] => issn-locals
[Value] => edsbas
)
[1] => Array
(
[Type] => issn-locals
[Value] => edsbas.oa
)
)
[Titles] => Array
(
[0] => Array
(
[TitleFull] => Human & Experimental Toxicology ; volume 40, issue 11, page 1955-1961 ; ISSN 0960-3271 1477-0903
[Type] => main
)
)
)
)
)
)
)
|
| IllustrationInfo |