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AuthorMadani, Aisha Y
AuthorMajeed, Yasser
AuthorAbdesselem, Houari B
AuthorAgha, Maha V
AuthorVakayil, Muneera
AuthorSukhun, Nour K Al
AuthorHalabi, Najeeb M
AuthorKumar, Pankaj
AuthorHayat, Shahina
AuthorElrayess, Mohamed A
AuthorRafii, Arash
AuthorSuhre, Karsten
AuthorMazloum, Nayef A
Available date2021-03-31T06:06:56Z
Publication Date2021-02-01
Publication NameAntioxidants
Identifierhttp://dx.doi.org/10.3390/antiox10020334
CitationMadani AY, Majeed Y, Abdesselem HB, Agha MV, Vakayil M, Sukhun NKA, Halabi NM, Kumar P, Hayat S, Elrayess MA, Rafii A, Suhre K, Mazloum NA. Signal Transducer and Activator of Transcription 3 (STAT3) Suppresses STAT1/Interferon Signaling Pathway and Inflammation in Senescent Preadipocytes. Antioxidants (Basel). 2021 Feb 23;10(2):334. doi: 10.3390/antiox10020334.
URIhttp://hdl.handle.net/10576/18040
AbstractObesity promotes premature aging and dysfunction of white adipose tissue (WAT) through the accumulation of cellular senescence. The senescent cells burden in WAT has been linked to inflammation, insulin-resistance (IR), and type 2 diabetes (T2D). There is limited knowledge about molecular mechanisms that sustain inflammation in obese states. Here, we describe a robust and physiologically relevant in vitro system to trigger senescence in mouse 3T3-L1 preadipocytes. By employing transcriptomics analyses, we discovered up-regulation of key pro-inflammatory molecules and activation of interferon/signal transducer and activator of transcription (STAT)1/3 signaling in senescent preadipocytes, and expression of downstream targets was induced in epididymal WAT of obese mice, and obese human adipose tissue. To test the relevance of STAT1/3 signaling to preadipocyte senescence, we used Clustered Regularly Interspaced Short Palindromic Repeats/CRISPR associated protein 9 (CRISPR/Cas9) technology to delete STAT1/3 and discovered that STAT1 promoted growth arrest and cooperated with cyclic Guanosine Monophosphate-Adenosine Monophosphate (GMP-AMP) synthase-stimulator of interferon genes (cGAS-STING) to drive the expression of interferon β (IFNβ), C-X-C motif chemokine ligand 10 (CXCL10), and interferon signaling-related genes. In contrast, we discovered that STAT3 was a negative regulator of STAT1/cGAS-STING signaling-it suppressed senescence and inflammation. These data provide insights into how STAT1/STAT3 signaling coordinates senescence and inflammation through functional interactions with the cGAS/STING pathway.
Languageen
PublisherMDPI
SubjectROS
SASP
cellular senescence
inflammation
preadipocytes
type 2 diabetes
TitleSignal Transducer and Activator of Transcription 3 (STAT3) Suppresses STAT1/Interferon Signaling Pathway and Inflammation in Senescent Preadipocytes.
TypeArticle
Issue Number2
Volume Number10
ESSN2076-3921
dc.accessType Open Access


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