Self-healing Behavior of Ethylene Propylene Diene Rubbers Based on Ionic Association

To meet the increasing demand for safe, environmentally friendly and high-performance smart materials, self-healing rubbers are highly desired. Here, the self-healing performance of ethylene propylene diene monomer rubber (EPDM) is reported, which was designed by graft-polymerization of zinc dimethacrylate (ZDMA) onto rubber chains to form a reversible ionic cross-linked network. Single ionic cross-linked network and dual network, combining covalent and ionic cross-links, could be tuned by controlling vulcanization process to achieve tailorable mechanical and self-healing properties. It was found that ionic cross-linked EPDM showed a recovery of more than 95% of the original mechanical strength through a healing process of 1 h at 100 °C. The covalent cross-links could improve mechanical properties but block self-healing. Adding 50 wt% liquid rubber to “dry” EPDM could effectively enhance self-healing capability of the dual cross-linked network and the healed tensile strength could reach 0.9 MPa. A compromise between mechanical performance and healing capability could be potentially tailored by controlling vulcanization process and liquid rubber content.

Follistatin-Like 1 Promotes Bleomycin-lnduced Pulmonary Fibrosis through the Transforming Growth Factor Beta 1/Mitogen-Activated Protein Kinase Signaling Pathway

Background： Follistatin-like I （FSTL 1） is a novel profibrogenic factor that induces pulmonary fibrosis （PF） through the transforming growth factor-beta 1 （TGF-[B 1 ）/Smad signaling. Little is known about its effects on PF through the non-Smad signaling, like the mitogen-activated protein kinase （MAPK） pathway. Therefore, this study aimed to investigate the role ofFSTL 1 in PF through the MAPK signaling pathway and its mechanisms in lung fibrogenesis. Methods： PF was induced in Fstll~ and wild-type （WT） C57BL/6 mice with bleomycin. After 14 days, the mice were sacrificed, and lung tissues were stained with hematoxylin and eosin; the hydroxyproline content was measured to confirm PF. The mRNA and protein level of FSTLI and the change of MAPK phosphorylation were measured by quantitative polymerase chain reaction and Western blotting. The effect of Fst11 deficiency on fibroblasts differentiation was measured by Western blotting and cell immunofluorescence. MAPK signaling activation was measured by Western blotting in Fst11＋/ and WT fibroblasts treated with recombinant human FSTLI protein. We pretreated mouse lung fibroblast cells with inhibitors of the extracellular signal-regulated kinase （ERK）, p38, and Jun N-terminal kinase （JNK） signaling and analyzed their differentiation, proliferation, migration, and invasion by Western blotting, 3-（4,5-dimethylthiazol-2-yl）-2,5-diphenyltetrazolium bromide analysis, and transwell assays. The Student＇s t-test was used to compare the differences between two groups. Results： Fstll deficiency attenuated phosphorylation of the ERK, p38, and JNK signaling in bleomycin-induced fibrotic lung tissue 14 days after injury （0.67 ± 0.05 vs. 1.22 ± 0.03, t = 14.92, P = 0.0001; 0.41 ± 0.01 vs. 1.15 ± 0.07; t = 11.19; P = 0.0004; and 0.41 ± 0.01 vs. 1.07± 0.07, t = 8.92, P = 0.0009; respectively）, compared with WT lungs at the same time and in primary lung fibroblasts （0.82 ± 0.01 vs. 1.01 ±0.04, t = 4.06, P = 0.0150; 1.04 ±0.03 vs. 1.24 ± 0.03, t= 4.44, P = 0.0100： and 0.76 ±0.05 vs. 0.99± 0.05, t = 4.48, P = 0.0100; respectively）, compared with TGF-β1-stimulated WT group. Recombinant human FSTLI protein in lung fibroblasts enhanced TG F-β1 -mediated phosphorylation of the ERK （ 1.19± 0.08 vs, 0.55 ± 0.04, t = 6.99, P = 0.0020）, p38 （ 1.18 ±0.04 vs. 0.66 ± 0.03, t = 11.20, P = 0.0020）, and .INK （ 1,11± 0.01 vs. 0.84 ± 0.04, t = 6.53, P = 0.0030）, compared with the TGF-β1-stimulated WT group. Fstll-deficient fibroblasts showed reduced alpha-smooth muscle actin （α-SMA） expression （0.70 ± 0.06 vs. 1.28 ±0.11, t = 4.65, P = 0.0035, compared with the untreated WT group; 1.40 ± 0.05 vs. 1.76± 0.02, t = 6.31, P = 0.0007; compared with the TGF-β1-treated WT group）. Compared with the corresponding condition in the control group, the TGF-β1/FSTL 1-mediated α-SMA expression was significantly suppressed by pretreatment with an inhibitor of p38 （0.73± 0.01 vs. 1.13 ± 0.10, t = 3.92, P = 0.0078） and JNK （0.78 ± 0.03 vs. 1.08 ± 0.06, t = 4.40,P = 0.0046） signaling. The proliferation of mouse lung fibroblast cells （MLgs） significantly decreased after treatment of an inhibitor of p38 （0.30 ±0.01 vs. 0.46 ±0.03, t = 4.64, P = 0.0009）, JNK （0.30 ± 0.01 vs. 0.49 ± 0.01, t = 12.84, P = 0.0001）, and Smad2/3 （0.18 ± 0.02 vs. 0.46 ±0.02, t = 12.69, P = 0.0001） signaling compared with the dimethylsulibxide group. The migration and invasion cells of MLgs significantly decreased in medium pretreated with an inhibitor of p38 （70.17 ±3.28 vs. 116.30 ± 7.11, t = 5.89, P = 0.0042 for the migratory cells; 19.87 ± 0.84 vs. 32.70 i 0.95, t =10.14, P = 0.0005 for the invasive cells）, JNK （72.30 ±3.85 vs. 116.30 ± 7.11, t = 5.44, P = 0.0056 for the migratory cells; 18.03 ± 0.94 vs. 32.70 ± 0.95, t = 11.00, P = 0.0004 for the invasive cells）, and Smad2/3 （64.76 ± 1.41 vs. 116.30 ± 7.11, t = 7.11, P = 0.0021 for the migratory cells; 18.03 ± 0.94 vs. 32.70 ±0.95, t = 13.29, P = 0.0002 for the invasive cells） signaling compared with the corresponding condition in the dimethylsulfoxide group. Conclusion： FSTL1 affects lung fibroblast differentiation, proliferation, migration, and invasion through p38 and JNK signaling, and in this way, it might influence the development of PF.