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AuthorMadani, Aisha Y.
AuthorMajeed, Yasser
AuthorAbdesselem, Houari B.
AuthorAgha, Maha V.
AuthorVakayil, Muneera
AuthorAl Sukhun, Nour K.
AuthorHalabi, Najeeb M.
AuthorKumar, Pankaj
AuthorHayat, Shahina
AuthorElrayess, Mohamed A.
AuthorRafii, Arash
AuthorSuhre, Karsten
AuthorMazloum, Nayef A.
Available date2021-03-09T06:45:50Z
Publication Date2021-02-01
Publication NameAntioxidants
Identifierhttp://dx.doi.org/10.3390/antiox10020334
CitationMadani, A.Y.; Majeed, Y.; Abdesselem, H.B.; Agha, M.V.; Vakayil, M.; Sukhun, N.K.A.; Halabi, N.M.; Kumar, P.; Hayat, S.; Elrayess, M.A.; Rafii, A.; Suhre, K.; Mazloum, N.A. Signal Transducer and Activator of Transcription 3 (STAT3) Suppresses STAT1/Interferon Signaling Pathway and Inflammation in Senescent Preadipocytes. Antioxidants 2021, 10, 334. https://doi.org/10.3390/antiox10020334
URIhttps://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85101241952&origin=inward
URIhttp://hdl.handle.net/10576/17876
Abstract© 2021 by the authors. Licensee MDPI, Basel, Switzerland. Obesity 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
SubjectCellular senescence
Inflammation
Preadipocytes
ROS
SASP
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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