Figure 6.

Interaction between Sirtuin 3 (SIRT3) and transforming growth factor beta 1 (TGFβ1) during fibrogenesis. (A) Real-time quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR) analysis for SMAD family member 3 (SMAD3) expression in SIRT3-deficient (Sirt3^−/−; n = 7 per treatment) and wild-type (WT; n = 5 per treatment) control mice after bleomycin (Bleo) or phosphate-buffered saline vehicle, at 14-day postexposure. (B) qRT-PCR confirmation for SMAD3 expression in normal human lung fibroblasts (NHLF) overexpressing SIRT3. **p < .01, ***p < .005. (C) Model for the role of SIRT3/TGFβ crosstalk in pulmonary fibrosis. The proposed model describes the role of SIRT3 in the regulation of SMAD3 and the antioxidant response during fibrogenesis. Aging, lung injury, TGFβ1 expression, genetic and environmental factors that contribute to reduction of SIRT3 favor the profibrotic effects of TGFβ1. By contrast, induction of SIRT3, by resveratrol, small molecules, or genetic approaches, enhances antifibrotic effects in the healthy lung mediated through downregulation of TGFβ1 signal transduction and an enhanced antioxidant response. Taken together, we propose that SIRT3 is critical to modulating the fibrotic response to lung injury in the elderly adults.