Glucocorticoids Recruit Tgfbr3 and Smad1 to Shift Transforming Growth Factor-β Signaling from the Tgfbr1/Smad2/3 Axis to the Acvrl1/Smad1 Axis in Lung Fibroblasts

Novel role of the clustered miR‐23b‐3p and miR‐27b‐3p in enhanced expression of fibrosis‐associated genes by targeting TGFBR3 in atrial fibroblasts

“…34 A synthetic peptide from TGFBR3, P144, was reported to efficiently inhibit the TGF-β1-dependent signalling pathway and collagen type I synthesis in cardiac fibroblasts. 34 A synthetic peptide from TGFBR3, P144, was reported to efficiently inhibit the TGF-β1-dependent signalling pathway and collagen type I synthesis in cardiac fibroblasts.…”

Transformujący czynnik wzrostu β1 (TGFβ1) i naczyniowo-śródbłonkowy czynnik wzrostu (VEGF) we krwi ludzi zdrowych i chorych z orbitopatią Gravesa — nowy mechanizm działania glikokortykosteroidów?

“…Glucocorticoids, including methylprednisolone in vitro potentiated TGFb signalling by the Smad1/5/8 signalling and blunted signalling by the Smad2/3 in primary lung fibroblasts, smooth muscle cells, and endothelial cells. Dexamethasone acted synergistically with TGFb to drive differentiation of primary lung fibroblasts to myofibroblasts, revealed by the acquisition of smooth muscle actin and smooth muscle myosin, which are exclusively Smad1-dependent processes in fibroblasts [67]. There are also interesting observations concerning the activity of glucocorticoids approved in the treatment of autoimmune diseases.…”

The cytokines of pulmonary fibrosis: Much learned, much more to learn

“…Both canonical and noncanonical TGF-b signaling pathways are inhibited by Smad6 and/ or Smad7 through a negative feedback loop [119]. Non-canonical signaling occurs through several other intracellular signaling molecules, including but not limited to endoglin/Smad1 [114,115,[120][121][122][123]; TRAF6 [119,[124][125][126]; ERK1/2 [115,121,[127][128][129][130], p38 [131,132] and JunB [133] MAPK; c-Abl [134]; mTOR [134]; PI3K/ AKT [115,128,132,135]; and NF-jB [136]. Much attention has additionally been directed recently to the Wnt/b-catenin pathway, which appears to promote proliferation and migration of lung fibroblasts and profibrotic gene expression [137,138], control TGF-b production and profibrotic activity [139,140], and facilitate EMT through direct interaction between Smad3 and b-catenin [141].…”