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. Author manuscript; available in PMC: 2018 Jul 1.
Published in final edited form as: Matrix Biol. 2016 Aug 6;60-61:86–95. doi: 10.1016/j.matbio.2016.08.001

Figure 4. Fluctuations of pro-angiogenic activity during TC-matrix remodeling.

Figure 4

a) TC-DNA is similar to c-DNA. Day 1: 1.27 ± 0.24, n = 6 vs. 1 ± 0.024, n = 6; Day 5: 3.97 ± 0.23, n = 6 vs. 3.26 ± 0.14, n = 6; Day 9: 4.34 ± 0.295, n = 6 vs. 4.43 ± 0.21, n= 5. MI/TC-DNA is significantly lower than TC-DNA at later time points, indicating that fewer cells attach to MMP-inhibited Fn-rich matrices. MI/TC-DNA Day 1: 1.08 ± 0.21, n = 6, MI/TC-DNA Day 5: 1.61 ± 0.34, n = 6; p < 0.0001 (TC-ECM & MI/TC-ECM), MI/TC-DNA Day 9: 1.84 ± 0.29, n = 6 vs. 4.34 ± 0.295, n = 6; p < 0.001 (TC-ECM & MI/TC-ECM). Mean ± SEM.

b) Over time, TC-VEGF secretion (normalized to DNA, then to 1d control) decreases, while MI/TC-VEGF secretion reaches a maximum at Day 5, when CAFs interact with a highly stretched/unfolded Fn-rich matrix. Day 1: 1.11 ± 0.11, n = 6 vs. 1 ± 0.03, n = 6, Day 5: 0.57 ± 0.06, n = 6 vs. 1.13 ± 0.28, n = 6, Day 9: 0.70 ± 0.18, n = 6 vs. 2.10 ± 0.56, n = 5; p < 0.05 (TC-ECM & c-ECM)). MI/TC-ECM Day 1: 0.66 ± 0.073, n = 6; p < 0.01 (c- & TC-ECM), MI/TC-ECM Day 5: 1.97 ± 0.15, n = 6; p < 0.05 (c-ECM); p < 0.0001 (TC-ECM), MI/TC-ECM Day 9: 0.78 ± 0.14, n = 6; p < 0.05 (c-ECM). Mean ± SEM.

c) Analysis of VEGF165 immobilization (normalized to Fn, with respect to 1d control) reveals that, although less VEGF binds to stretched/unfolded TC-Fn fibers (Day 1 and Day 5), TC-VEGF sequestration increases over time, which could partly explain the simultaneous decrease of soluble VEGF levels detected in TC samples (panel b). Day 1: 0.88 ± 0.02, n=7 vs. 1 ± 0.02, n = 7; p < 0.001, Day 5: 1.20 ± 0.08, n = 5 vs. 1.42 ± 0.02, n = 5; p < 0.05, Day 9: 1.66 ± 0.13, n = 6 vs. 1.16 ± 0.08, n = 6; p < 0.01 (TC-ECM & c-ECM)). MI/TC-ECM Day 1: 0.82 ± 0.03, n = 7; p < 0.001 (c-ECM), MI/TC-ECM Day 5: 0.74 ± 0.01, n = 6; p < 0.001 (c-ECM); p <0.001 (TC-ECM), MI/TC-ECM Day 9: 1.02 ± 0.06, n = 6; p < 0.01 (TC-ECM). Mean ± SEM.