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. Author manuscript; available in PMC: 2021 Aug 1.
Published in final edited form as: Matrix Biol. 2020 Mar 12;90:79–108. doi: 10.1016/j.matbio.2020.02.004

Fig. 8. Exogenous gremlin-1 treatment of FNcKO capsular bags rescues the defect in TGFβ signaling and fibrotic marker expression PCS.

Fig. 8.

(A) At 0 h PCS, little expression of gremlin-1 protein is detected in both WT and FNcKO LCs. However, by 48 h PCS, gremlin-1 protein expression is elevated in both WT (***P ≤ 0.001) and FNcKO LCs (***P ≤ 0.001) although the expression is significantly less in FNcKO LCs (**P = 0.004) compared to WT. In contrast, gremlin-1 levels are greatly attenuated in FNcKO LCs by 5 days PCS (***P ≤ 0.001) compared to WT whereas WT LCs maintain the robust expression of gremlin-1 (***P ≤ 0.001). Gremlin-1 (red) is merged with αSMA (green) and DNA detected by Draq5 (blue). Scale bars: 35 μm. LC, remnant lens epithelial cells/lens cells; C, lens capsule. All experiments had N = 3. Values are expressed as mean ± SEM. Asterisks (*) indicate statistically significant MFI between WT and FNcKO at a PCS or between two PCS time points. (B) Administration of exogenous gremlin-1 to FNcKO capsular bags elevates the levels of the fibrotic proteins αSMA (*P = 0.015), tenascin C (**P = 0.002), and collagen I (*P = 0.017) concomitant with elevated levels of pSMAD2/3 levels (*P = 0.013) at 5 days PCS. In contrast, exogenous gremlin-1 treatment did not reduce pSMAD1/5/8 levels in FNcKO capsular bags (P = 0.440). Collagen I, Tenascin C, pSMAD2/3 (downstream of TGFβ signaling), pSMAD1/5/8 (downstream of BMP signaling) (red), αSMA (green) and DNA detected by Draq5 (blue). Scale bars: 35 μm. LC, remnant lens epithelial cells/lens cells; C, lens capsule. All experiments had N = 3. Values are expressed as mean ± SEM. Asterisks (*) indicate statistically significant MFI between WT and/or FNcKO and/or FNcKO (gremlin-1) at 5 days PCS..