Additional file 2: Figure S2. of Inhibition of MMP-2 and MMP-9 decreases cellular migration, and angiogenesis in in vitro models of retinoblastoma

Weri-1 Rb cells are sensitive to MMPI. Weri-1 cells were cultured in the presence or absence of MMPI. The MMPI were used at a concentration range of 500 nM to 25 μM for up to 120 h. MTS proliferation solution was added to each well at a concentration of 10 μL solution per 100 μL at specific time points (0-, 48-, 72-, 96-, and 120-h) and incubated at 37 °C/5%CO2 for 2 h prior to reading on an absorbance reader. Values represent are optical density (O.D.) ± SEM at 482 nm with a reference wavelength of 630 nm. (TIFF 374 kb

DataSheet_1_IL11-mediated stromal cell activation may not be the master regulator of pro-fibrotic signaling downstream of TGFβ.pdf

Fibrotic diseases, such as idiopathic pulmonary fibrosis (IPF) and systemic scleroderma (SSc), are commonly associated with high morbidity and mortality, thereby representing a significant unmet medical need. Interleukin 11 (IL11)-mediated cell activation has been identified as a central mechanism for promoting fibrosis downstream of TGFβ. IL11 signaling has recently been reported to promote fibroblast-to-myofibroblast transition, thus leading to various pro-fibrotic phenotypic changes. We confirmed increased mRNA expression of IL11 and IL11Rα in fibrotic diseases by OMICs approaches and in situ hybridization. However, the vital role of IL11 as a driver for fibrosis was not recapitulated. While induction of IL11 secretion was observed downstream of TGFβ signaling in human lung fibroblasts and epithelial cells, the cellular responses induced by IL11 was quantitatively and qualitatively inferior to that of TGFβ at the transcriptional and translational levels. IL11 blocking antibodies inhibited IL11Rα-proximal STAT3 activation but failed to block TGFβ-induced profibrotic signals. In summary, our results challenge the concept of IL11 blockade as a strategy for providing transformative treatment for fibrosis.</p