Fig. 11.

Fibroblasts in db/db hearts show increased collagen synthesis. A and B: cryosections from 6-mo-old lean wild-type (WT) and db/db mouse hearts were stained with an anticollagen type I antibody. DAPI counterstaining was used to identify collagen type I-expressing interstitial cells. C: db/db hearts had a higher density of collagen type I-expressing interstitial cells that did not reach statistical significance (n = 8 hearts/group, P = 0.05). D: sex-specific analysis showed a trend toward higher density of collagen type I-expressing cells in female db/db hearts (n = 4 hearts/group). E and F: in vitro, cardiac fibroblasts harvested from 4-mo-old db/db mice had a 2.0- to 3.0-fold increase in baseline collagen type I (E) and type III (F) mRNA expression compared with fibroblasts from WT hearts. Activated fibroblasts from db/db hearts were less responsive to transforming growth factor (TGF)-β₁ stimulation. TGF-β₁ (10 ng/ml) stimulation for 4 h stimulated collagen type I and type III mRNA synthesis in WT cells but did not significantly increase expression of collagens in db/db fibroblasts (n = 7–8/group). Scale bar = 25 μm. **P < 0.01, ^P < 0.05, and ^^P < 0.01 vs. corresponding unstimulated cells. F, female; M, male.