BMSC-derived exosomes ameliorate sulfur mustard-induced acute lung injury by regulating the GPRC5A–YAP axis

Butt Y, Kurdowska A, Allen TC. Acute lung injury: a clinical and molecular review. Arch Pathol Lab Med. 2016;140:345–50.

CAS  PubMed  Article  PubMed Central  Google Scholar 

Matthay MA, Zemans RL, Zimmerman GA, Arabi YM, Beitler JR, Mercat A, et al. Acute respiratory distress syndrome. Nat Rev Dis Primers. 2019;5:18.

PubMed  PubMed Central  Article  Google Scholar 

Spadaro S, Park M, Turrini C, Tunstall T, Thwaites R, Mauri T, et al. Biomarkers for acute respiratory distress syndrome and prospects for personalised medicine. J Inflamm. 2019;16:1.

Article  Google Scholar 

Ghabili K, Agutter PS, Ghanei M, Ansarin K, Panahi Y, Shoja MM. Sulfur mustard toxicity: history, chemistry, pharmacokinetics, and pharmacodynamics. Crit Rev Toxicol. 2011;41:384–403.

CAS  PubMed  Article  PubMed Central  Google Scholar 

Sun M, Yang Y, Meng W, Xu Q, Lin F, Chen Y, et al. Advanced biotherapy for the treatment of sulfur mustard poisoning. Chem-Biol Interact. 2018;286:111–8.

CAS  PubMed  Article  PubMed Central  Google Scholar 

Weinberger B, Malaviya R, Sunil VR, Venosa A, Heck DE, Laskin JD, et al. Mustard vesicant-induced lung injury: advances in therapy. Toxicol Appl Pharmacol. 2016;305:1–11.

CAS  PubMed  PubMed Central  Article  Google Scholar 

Nejad-Moghaddam A, Ajdari S, Tahmasbpour E, Goodarzi H, Panahi Y, Ghanei M. Adipose-derived mesenchymal stem cells for treatment of airway injuries in a patient after long-term exposure to sulfur mustard. Cell J. 2017;19:117–26.

PubMed  PubMed Central  Google Scholar 

Simonson OE, Mougiakakos D, Heldring N, Bassi G, Johansson HJ, Dalen M, et al. In vivo effects of mesenchymal stromal cells in two patients with severe acute respiratory distress syndrome. Stem Cells Transl Med. 2015;4:1199–213.

CAS  PubMed  PubMed Central  Article  Google Scholar 

Matthay MA, Calfee CS, Zhuo H, Thompson BT, Wilson JG, Levitt JE, et al. Treatment with allogeneic mesenchymal stromal cells for moderate to severe acute respiratory distress syndrome (START study): a randomised phase 2a safety trial. Lancet Respir Med. 2019;7:154–62.

Article  Google Scholar 

Feng Y, Xu Q, Yang Y, Shi W, Meng W, Zhang H, et al. The therapeutic effects of bone marrow-derived mesenchymal stromal cells in the acute lung injury induced by sulfur mustard. Stem Cell Res Ther. 2019;10:90.

CAS  PubMed  PubMed Central  Article  Google Scholar 

Lee HY, Hong IS. Double-edged sword of mesenchymal stem cells: cancer-promoting versus therapeutic potential. Cancer Sci. 2017;108:1939–46.

CAS  PubMed  PubMed Central  Article  Google Scholar 

Abraham A, Krasnodembskaya A. Mesenchymal stem cell-derived extracellular vesicles for the treatment of acute respiratory distress syndrome. Stem Cells Transl Med. 2020;9:28–38.

CAS  PubMed  Article  PubMed Central  Google Scholar 

Monsel A, Zhu YG, Gudapati V, Lim H, Lee JW. Mesenchymal stem cell derived secretome and extracellular vesicles for acute lung injury and other inflammatory lung diseases. Expert Opin Biol Ther. 2016;16:859–71.

CAS  PubMed  PubMed Central  Article  Google Scholar 

Li X, Liu L, Yang J, Yu Y, Chai J, Wang L, et al. Exosome derived from human umbilical cord mesenchymal stem cell mediates miR-181c attenuating burn-induced excessive inflammation. EBioMedicine. 2016;8:72–82.

PubMed  PubMed Central  Article  Google Scholar 

Zhang B, Shi Y, Gong A, Pan Z, Shi H, Yang H, et al. HucMSC exosome-delivered 14-3-3zeta orchestrates self-control of the Wnt response via modulation of YAP during cutaneous regeneration. Stem Cells. 2016;34:2485–500.

CAS  PubMed  Article  PubMed Central  Google Scholar 

Hao Q, Zhu YG, Monsel A, Gennai S, Lee T, Xu F, et al. Study of bone marrow and embryonic stem cell-derived human mesenchymal stem cells for treatment of Escherichia coli endotoxin-induced acute lung injury in mice. Stem Cells Transl Med. 2015;4:832–40.

CAS  PubMed  PubMed Central  Article  Google Scholar 

Park J, Kim S, Lim H, Liu A, Hu S, Lee J, et al. Therapeutic effects of human mesenchymal stem cell microvesicles in an ex vivo perfused human lung injured with severe E. coli pneumonia. Thorax. 2019;74:43–50.

PubMed  PubMed Central  Article  Google Scholar 

Han J, Liu Y, Liu H, Li Y. Genetically modified mesenchymal stem cell therapy for acute respiratory distress syndrome. Stem Cell Res Ther. 2019;10:386.

PubMed  PubMed Central  Article  Google Scholar 

Yan Y, Jiang W, Tan Y, Zou S, Zhang H, Mao F, et al. HucMSC exosome-derived GPX1 is required for the recovery of hepatic oxidant injury. Mol Ther. 2017;25:465–79.

CAS  PubMed  PubMed Central  Article  Google Scholar 

Sawyer TW. N-acetylcysteine as a treatment for sulphur mustard poisoning. Free Radic Biol Med. 2020;161:305–20.

CAS  PubMed  PubMed Central  Article  Google Scholar 

Dong L, He HL, Lu XM, Yang Y, Qiu HB. Modulation of FLT3 signaling targets conventional dendritic cells to attenuate acute lung injury. APMIS. 2012;120:808–18.

CAS  PubMed  Article  PubMed Central  Google Scholar 

Bachler G, Losert S, Umehara Y, von Goetz N, Rodriguez-Lorenzo L, Petri-Fink A, et al. Translocation of gold nanoparticles across the lung epithelial tissue barrier: combining in vitro and in silico methods to substitute in vivo experiments. Part Fibre Toxicol. 2015;12:18.

PubMed  PubMed Central  Article  CAS  Google Scholar 

Schwarz BT, Wang F, Shen L, Clayburgh DR, Su L, Wang Y, et al. LIGHT signals directly to intestinal epithelia to cause barrier dysfunction via cytoskeletal and endocytic mechanisms. Gastroenterology. 2007;132:2383–94.

CAS  PubMed  PubMed Central  Article  Google Scholar 

Shen CH, Lin JY, Chang YL, Wu SY, Peng CK, Wu CP, et al. Inhibition of NKCC1 modulates alveolar fluid clearance and inflammation in ischemia-reperfusion lung injury via TRAF6-mediated pathways. Front Immunol. 2018;9:2049.

PubMed  PubMed Central  Article  CAS  Google Scholar 

Xu Q, Shi W, Lv P, Meng W, Mao G, Gong C, et al. Critical role of caveolin-1 in aflatoxin B1-induced hepatotoxicity via the regulation of oxidation and autophagy. Cell Death Dis. 2020;11:6.

CAS  PubMed  PubMed Central  Article  Google Scholar 

Soni S, Wilson MR, O’Dea KP, Yoshida M, Katbeh U, Woods SJ, et al. Alveolar macrophage-derived microvesicles mediate acute lung injury. Thorax. 2016;71:1020–9.

PubMed  PubMed Central  Article  Google Scholar 

Meng W, Sun M, Xu Q, Cen J, Cao Y, Li Z, et al. Development of a series of fluorescent probes for the early diagnostic imaging of sulfur mustard poisoning. ACS Sens. 2019;4:2794–801.

CAS  PubMed  Article  PubMed Central  Google Scholar 

Gu C, Liu M, Zhao T, Wang D, Wang Y. Protective role of p120-catenin in maintaining the integrity of adherens and tight junctions in ventilator-induced lung injury. Respir Res. 2015;16:58.

PubMed  PubMed Central  Article  CAS  Google Scholar 

Liao Y, Song H, Xu D, Jiao H, Yao F, Liu J, et al. Gprc5a-deficiency confers susceptibility to endotoxin-induced acute lung injury via NF-kappaB pathway. Cell Cycle. 2015;14:1403–12.

CAS  PubMed  PubMed Central  Article  Google Scholar 

Kim J, Kim YH, Park DY, Bae H, Lee DH, Kim KH, et al. YAP/TAZ regulates sprouting angiogenesis and vascular barrier maturation. J Clin Invest. 2017;127:3441–61.

PubMed  PubMed Central  Article  Google Scholar 

LaCanna R, Liccardo D, Zhang P, Tragesser L, Wang Y, Cao T, et al. Yap/Taz regulate alveolar regeneration and resolution of lung inflammation. J Clin Invest. 2019;129:2107–22.

PubMed  PubMed Central  Article  Google Scholar 

Etemad L, Moshiri M, Balali-Mood M. Advances in treatment of acute sulfur mustard poisoning—a critical review. Crit Rev Toxicol. 2019;49:191–214.

PubMed  Article  PubMed Central  Google Scholar 

Wolfe GA, Petteys SM, Phelps JF, Wasmund JB, Plackett TP. Sulfur mustard exposure: review of acute, subacute, and long-term effects and their management. J Spec Oper Med. 2019;19:81–6.

PubMed  PubMed Central  Google Scholar 

Lee JW, Fang X, Krasnodembskaya A, Howard JP, Matthay MA. Concise review: mesenchymal stem cells for acute lung injury: role of paracrine soluble factors. Stem Cells. 2011;29:913–9.

CAS  PubMed  PubMed Central  Article  Google Scholar 

Zheng G, Huang L, Tong H, Shu Q, Hu Y, Ge M, et al. Treatment of acute respiratory distress syndrome with allogeneic adipose-derived mesenchymal stem cells: a randomized, placebo-controlled pilot study. Respir Res. 2014;15:39.

PubMed  PubMed Central  Article  CAS  Google Scholar 

Yan X, Shu Y, He J, Zhao J, Jia L, Xie J, et al. Therapeutic effects of human umbilical cord mesenchymal stromal cells in Sprague-Dawley rats with percutaneous exposure to sulfur mustard. Stem Cells Dev. 2019;28:69–80.

CAS  PubMed  Article  PubMed Central  Google Scholar 

Witwer KW, Van Balkom BWM, Bruno S, Choo A, Dominici M, Gimona M, et al. Defining mesenchymal stromal cell (MSC)-derived small extracellular vesicles for therapeutic applications. J Extracell Vesicles. 2019;8:1609206.

CAS  PubMed  PubMed Central  Article  Google Scholar 

Heinrich A, Balszuweit F, Thiermann H, Kehe K. Rapid simultaneous determination of apoptosis, necrosis, and viability in sulfur mustard exposed HaCaT cell cultures. Toxicol Lett. 2009;191:260–7.

CAS  PubMed  Article  Google Scholar 

Lang S, Popp T, Kriegs CS, Schmidt A, Balszuweit F, Menacher G, et al. Anti-apoptotic and moderate anti-inflammatory effects of berberine in sulfur mustard exposed keratinocytes. Toxicol Lett. 2018;293:2–8.

CAS  PubMed  Article  PubMed Central  Google Scholar 

Janga H, Cassidy L, Wang F, Spengler D, Oestern-Fitschen S, Krause MF, et al. Site-specific and endothelial-mediated dysfunction of the alveolar-capillary barrier in response to lipopolysaccharides. J Cell Mol Med. 2018;22:982–98.

CAS  PubMed  PubMed Central  Google Scholar 

Higuita-Castro N, Nelson MT, Shukla V, Agudelo-Garcia PA, Zhang W, Duarte-Sanmiguel SM, et al. Using a novel microfabricated model of the alveolar-capillary barrier to investigate the effect of matrix structure on atelectrauma. Sci Rep. 2017;7:11623.

CAS  PubMed  PubMed Central  Article  Google Scholar 

Short KR, Kasper J, van der Aa S, Andeweg AC, Zaaraoui-Boutahar F, Goeijenbier M, et al. Influenza virus damages the alveolar barrier by disrupting epithelial cell tight junctions. Eur Respir J. 2016;47:954–66.

CAS  PubMed  Article  PubMed Central  Google Scholar 

Cai J, Culley MK, Zhao Y, Zhao J. The role of ubiquitination and deubiquitination in the regulation of cell junctions. Protein Cell. 2018;9:754–69.

CAS  PubMed  Article  PubMed Central  Google Scholar 

Stamatovic SM, Johnson AM, Sladojevic N, Keep RF, Andjelkovic AV. Endocytosis of tight junction proteins and the regulation of degradation and recycling. Ann N Y Acad Sci. 2017;1397:54–65.

CAS  PubMed  PubMed Central  Article  Google Scholar 

Sumi A, Hayes P, D’Angelo A, Colombelli J, Salbreux G, Dierkes K, et al. Adherens junction length during tissue contraction is controlled by the mechanosensitive activity of actomyosin and junctional recycling. Dev Cell. 2018;47:453–63 e3.

CAS  PubMed  PubMed Central  Article  Google Scholar 

Gonda A, Kabagwira J, Senthil GN, Wall NR. Internalization of exosomes through receptor-mediated endocytosis. Mol Cancer Res. 2019;17:337–47.

CAS  PubMed  Article  PubMed Central  Google Scholar 

Kotmakçı M, Bozok, Çetintaş V. Extracellular vesicles as natural nanosized delivery systems for small-molecule drugs and genetic material: steps towards the future nanomedicines. J Pharm Pharm Sci. 2015;18:396–413.

PubMed  Article  PubMed Central  Google Scholar 

Park K-S, Bandeira E, Shelke GV, Lässer C, Lötvall J. Enhancement of therapeutic potential of mesenchymal stem cell-derived extracellular vesicles. Stem Cell Res Ther. 2019;10:288.

PubMed  PubMed Central  Article  CAS  Google Scholar 

Mendt M, Rezvani K, Shpall E. Mesenchymal stem cell-derived exosomes for clinical use. Bone Marrow Transpl. 2019;54:789–92.

Article  Google Scholar 

Harrell CR, Jovicic N, Djonov V, Volarevic V. Therapeutic use of mesenchymal stem cell-derived exosomes: from basic science to clinics. Pharmaceutics. 2020;12:474.

Tao Q, Fujimoto J, Men T, Ye X, Deng J, Lacroix L, et al. Identification of the retinoic acid-inducible Gprc5a as a new lung tumor suppressor gene. J Natl Cancer Inst. 2007;99:1668–82.

CAS  PubMed  Article  PubMed Central  Google Scholar 

Wang J, Farris AB, Xu K, Wang P, Zhang X, Duong DM, et al. GPRC5A suppresses protein synthesis at the endoplasmic reticulum to prevent radiation-induced lung tumorigenesis. Nat Commun. 2016;7:11795.

CAS  PubMed  PubMed Central  Article  Google Scholar 

Huang Z, Wang S, Liu Y, Fan L, Zeng Y, Han H, et al. GPRC5A reduction contributes to pollutant benzo[a]pyrene injury via aggravating murine fibrosis, leading to poor prognosis of IIP patients. Sci Total Environ. 2020;739:139923.

CAS  PubMed  Article  PubMed Central  Google Scholar 

Kantrowitz J, Sinjab A, Xu L, McDowell TL, Sivakumar S, Lang W, et al. Genome-wide gene expression changes in the normal-appearing airway during the evolution of smoking-associated lung adenocarcinoma. Cancer Prev Res. 2018;11:237–48.

CAS  Article  Google Scholar 

Greenhough A, Bagley C, Heesom KJ, Gurevich DB, Gay D, Bond M, et al. Cancer cell adaptation to hypoxia involves a HIF-GPRC5A-YAP axis. EMBO Mol Med. 2018;10:e8699.

Cao Z, Xu T, Tong X, Wang Y, Zhang D, Gao D, et al. Maternal yes-associated protein participates in porcine bastocyst development via modulation of trophectoderm epithelium barrier function. Cells. 2019;8:1606.