Figure 4: Conditional deletion of ADRA1D in myofibroblasts attenuates fibrosis.

Utilizing a myofibroblast-specific knockout approach, Acta2-CreERT2 mice were crossed with Adra1d^f/f mice (A) to produce Acta2-CreERT2; Adra1d^f/f offspring. (B, C) A targeted reduction in Adra1d expression within Zs+ (ACTA2+) cells (C, P = 0.0150). (D) Acta2-CreERT2; Adra1d^f/f mice received tamoxifen or vehicle timed to delete ADRA1D 7 days after bleomycin administration. (E-G) Specific deletion of ADRA1D in α-SMA-expressing cells results in reduced collagen deposition (E, P = 0.0024) and improved trichrome staining (F, G). Images were captured at 20x magnification. Data are presented as mean ± SEM or median ± IQR, with statistical tests including Student’s t-test for normally distributed data and Mann-Whitney for non-normally distributed data. *P < 0.01, **P < 0.01. ADRA1D, α1-adrenoreceptor subtype D; α-SMA, alpha-smooth muscle actin; TAM, tamoxifen; Zs, ZsGreen.