2026-10-13T07:46:34Z https://api.figshare.com/v2/oai

oai:figshare.com:article/34020945 2026-09-30T14:27:11Z category_30881 portal_1044 item_type_3 month_year_09_2026

REV-ERB α/β disruption drives Environmental Tobacco Smoke-induced senescence through a cGAS-STING signaling promoting lung Sadiya Bi Shaikh (23124112) Md Imam Faizan (23764776) Khursheed Ul Islam Ganaie (25135056) Karen Lin (25135073) Qixin Wang (24279943) Jennifer Becker (508221) Md Sohanur Rahman (18615271) Kingshuk Panda (19496470) Srinivasan Chinnapaiyan (19496467) Dongmei Li (22176721) Hoshang J. Unwalla (19496473) Irfan Rahman (22176835) Biological sciences Cigarette Smoke CLOCK Senescence cGAS-STING Fibroblast <p dir="ltr">Environmental exposures, such as cigarette and tobacco smoke disrupt pulmonary homeostasis and promote progressive remodeling and inflammation that increase susceptibility to chronic lung diseases. While cellular senescence and DNA damage are recognized contributors to smoke-induced lung injury, how these processes integrate with circadian regulation and innate immune sensing remain incompletely understood. Here, we identify a conserved multi-lineage transcriptional program in murine lungs that we define as the SCPS axis, characterized by Suppressed Circadian Clock Signaling, primed senescence, fibrinolytic shutdown, and activation of the cGAS-STING pathway. Using Rev-erbα/β^floxed mice, we show that environmental cigarette/tobacco smoke exposure induces robust senescence and SASP factor production in both epithelial and fibroblast populations, even in the presence of an intact molecular clock. Spatial transcriptomic analysis of smoker lungs demonstrates parallel alterations marked by increased expression of senescence-associated genes (CDKN1A, SERPINE1), activation of DNA damage and innate immune sensors (TREX1, TMEM173), and repression of core clock genes (ARNTL, PER2, NR1D1), particularly within AT2 cells and fibroblasts. Pharmacological clearance of senescent cells using the BCL-2 inhibitor ABT-263 effectively reverses these molecular and cellular phenotypes. Together, these findings reveal early epithelial remodeling and fibrotic priming during environmental smoke exposure and establish a mechanistic link between senescence, circadian disruption, and innate immune activation through the cGAS-STING pathway. The SCPS axis, therefore, represents an early molecular checkpoint of fibrotic susceptibility and a potential therapeutic target in environmentally driven lung injury.</p> 2026-09-30T14:27:11Z Dataset Dataset 10.60593/ur.d.34020945.v1 https://figshare.com/articles/dataset/REV-ERB_disruption_drives_Environmental_Tobacco_Smoke-induced_senescence_through_a_cGAS-STING_signaling_promoting_lung/34020945 CC BY 4.0