*4.7. LC-MS Analysis*

LC-MS analyses were done as described elsewhere [40]. Briefly, peptide samples were separated with a nano-flow ultrahigh pressure liquid chromatography system (RSLC, Thermo Scientific) equipped with a trapping column (3 μm C18 particle, 2 cm length, 75 μm ID, Acclaim PepMap, Thermo Scientific) and a 50 cm separation column (2 μm C18 particle, 75 μm ID, Acclaim PepMap, Thermo Scientific). Peptide mixtures were injected, enriched, and desalted on the trapping column at a flow rate of 6 μL/min with 0.1% TFA for 5 min. The trapping column was switched online with the separating column and peptides were eluted from the separating column with a multi-step binary gradient of buffer A (0.1% formic acid) and buffer B (80% ACN, 0.1% formic acid). The flow rate was 250 nL/min and the column temperature was set to 45◦C. The RSLC system was coupled online via a Nano Spray Flex Ion Soure II (Thermo Scientific) to an LTQ-Orbitrap Velos mass spectrometer that was operated in data-dependent acquisition mode. Overview scans were acquired at a resolution of 60k in the orbitrap analyzer. The top 10 most intensive ions were selected for CID fragmentation in the LTQ. Active exclusion was activated so that ions fragmented once were excluded from further fragmentation for 70 s within a mass window of 10 ppm of the specific m/z value.

The raw data were processed using Max Quant software [41] and the entries of mouse uniprot data base, including common contaminants. The proteins were identified by a false discovery rate of 0.01 on protein and peptide level and quantified by extracted ion chromatograms of all peptides. Data visualizations were done with Perseus [42] and GraphPad Prism software.

### *4.8. Statistical Analysis*

Statistical analyses were conducted with the SigmaPlot software (SYSTAT Software Inc; San Jose, USA) by a two-way analysis of variance (ANOVA) followed by a pair-wise comparison with Bonferroni-test. The data that were not normally distributed were subject to a ln or square root transformation. If data normalization failed, ANOVA on Ranks followed by a Mann–Whitney U *t*-test with a Bonferroni correction was performed.

#### **Supplementary Materials:** Supplementary materials can be found at http://www.mdpi.com/1422-0067/21/3/822/s1.

**Author Contributions:** J.C.J., J.F., T.T., C.M. and C.B. designed study, J.C.J., J.F., A.P., J.V. and C.B. performed experiments, J.C.J., J.F., A.P. and C.B. analyzed the results, J.C.J., T.T., C.M. and C.B. interpreted the results, J.C.J., A.P. and C.B. designed figures, C.B. drafted the manuscript, all authors edited and approved the manuscript. All authors have read and agreed to the published version of the manuscript

**Funding:** The project was funded by the Bundesministerium für Bildung und Forschung (BMBF) via the German Center for Lung Research (DZL) and the cluster of excellence "From Regenerative Biology to Reconstructive Therapy" (REBIRTH).

**Acknowledgments:** We thank Rita Lichatz, Susanne Kuhlmann, Annette Just and Melanie Bornemann for their excellent technical assistance.

**Conflicts of Interest:** Thomas Thum filed and licensed noncoding RNA patents (including miR-21). Thomas Thum is founder and shareholder of Cardior Pharmaceuticals GmbH.
