Regulation of JAM2 Expression in the Lungs of Streptozotocin-Induced Diabetic Mice and Human Pluripotent Stem Cell-Derived Alveolar Organoids

Overview

Journal Biomedicines

Specialty Biomedical Engineering

Date 2020 Sep 16

PMID 32932992

Citations 5

Authors

Roya Rasaei

Eunbi Kim

Ji-Young Kim

Sunghun Na

Jung-Hyun Kim

Jinbeom Heo

Dong-Myung Shin

Sun Shim Choi

Seok-Ho Hong

Affiliations

Soon will be listed here.

Abstract

Hyperglycemia is a causative factor in the pathogenesis of respiratory diseases, known to induce fibrosis and inflammation in the lung. However, little attention has been paid to genes related to hyperglycemic-induced lung alterations and stem cell applications for therapeutic use. In this study, our microarray data revealed significantly increased levels of junctional adhesion molecule 2 (JAM2) in the high glucose (HG)-induced transcriptional profile in human perivascular cells (hPVCs). The elevated level of JAM2 in HG-treated hPVCs was transcriptionally and epigenetically reversible when HG treatment was removed. We further investigated the expression of JAM2 using in vivo and in vitro hyperglycemic models. Our results showed significant upregulation of JAM2 in the lungs of streptozotocin (STZ)-induced diabetic mice, which was greatly suppressed by the administration of conditioned medium obtained from human mesenchymal stem cell cultures. Furthermore, JAM2 was found to be significantly upregulated in human pluripotent stem cell-derived multicellular alveolar organoids by exposure to HG. Our results suggest that JAM2 may play an important role in STZ-induced lung alterations and could be a potential indicator for predicting the therapeutic effects of stem cells and drugs in diabetic lung complications.

Citing Articles

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Human pluripotent stem-cell-derived alveolar organoids for modeling pulmonary fibrosis and drug testing.

Kim J, An G, Kim J, Rasaei R, Kim W, Jin X Cell Death Discov. 2021; 7(1):48.

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Altered Gene Expression Profiles in the Lungs of Streptozotocin-induced Diabetic Mice.

Kim J, Rasaei R, Park S, Kim J, Na S, Hong S Dev Reprod. 2020; 24(3):197-205.

PMID: 33110951 PMC: 7576965. DOI: 10.12717/DR.2020.24.3.197.

References

Park M, Hong S, Park S, Kim Y, Yang S, Kim H . Perivascular Stem Cell-Derived Cyclophilin A Improves Uterine Environment with Asherman's Syndrome via HIF1α-Dependent Angiogenesis. Mol Ther. 2020; 28(8):1818-1832. PMC: 7403347. DOI: 10.1016/j.ymthe.2020.05.015. View

Sabry D, Mohamed A, Monir M, Ibrahim H . The Effect of Mesenchymal Stem Cells Derived Microvesicles on the Treatment of Experimental CCL4 Induced Liver Fibrosis in Rats. Int J Stem Cells. 2019; 12(3):400-409. PMC: 6881047. DOI: 10.15283/ijsc18143. View

Kolahian S, Leiss V, Nurnberg B . Diabetic lung disease: fact or fiction?. Rev Endocr Metab Disord. 2019; 20(3):303-319. PMC: 7102037. DOI: 10.1007/s11154-019-09516-w. View

Heo J, Noh B, Lee S, Lee H, Kim Y, Lim J . Phosphorylation of TFCP2L1 by CDK1 is required for stem cell pluripotency and bladder carcinogenesis. EMBO Mol Med. 2019; 12(1):e10880. PMC: 6949511. DOI: 10.15252/emmm.201910880. View

Christen S, Coppieters K, Rose K, Holdener M, Bayer M, Pfeilschifter J . Blockade but not overexpression of the junctional adhesion molecule C influences virus-induced type 1 diabetes in mice. PLoS One. 2013; 8(1):e54675. PMC: 3556033. DOI: 10.1371/journal.pone.0054675. View

Strikoudis A, Cieslak A, Loffredo L, Chen Y, Patel N, Saqi A . Modeling of Fibrotic Lung Disease Using 3D Organoids Derived from Human Pluripotent Stem Cells. Cell Rep. 2019; 27(12):3709-3723.e5. PMC: 6594401. DOI: 10.1016/j.celrep.2019.05.077. View

Hong S, Rampalli S, Lee J, McNicol J, Collins T, Draper J . Cell fate potential of human pluripotent stem cells is encoded by histone modifications. Cell Stem Cell. 2011; 9(1):24-36. DOI: 10.1016/j.stem.2011.06.002. View

Leibel S, Winquist A, Tseu I, Wang J, Luo D, Shojaie S . Reversal of Surfactant Protein B Deficiency in Patient Specific Human Induced Pluripotent Stem Cell Derived Lung Organoids by Gene Therapy. Sci Rep. 2019; 9(1):13450. PMC: 6748939. DOI: 10.1038/s41598-019-49696-8. View

Ho B, Pek N, Soh B . Disease Modeling Using 3D Organoids Derived from Human Induced Pluripotent Stem Cells. Int J Mol Sci. 2018; 19(4). PMC: 5979503. DOI: 10.3390/ijms19040936. View

10.

Chen Y, Zhang F, Wang D, Li L, Si H, Wang C . Mesenchymal Stem Cells Attenuate Diabetic Lung Fibrosis via Adjusting Sirt3-Mediated Stress Responses in Rats. Oxid Med Cell Longev. 2020; 2020:8076105. PMC: 7024095. DOI: 10.1155/2020/8076105. View

11.

Hintermann E, Bayer M, Conti C, Fuchs S, Fausther M, Leung P . Junctional adhesion molecules JAM-B and JAM-C promote autoimmune-mediated liver fibrosis in mice. J Autoimmun. 2018; 91:83-96. DOI: 10.1016/j.jaut.2018.05.001. View

12.

Guo Y, Yu Y, Hu S, Chen Y, Shen Z . The therapeutic potential of mesenchymal stem cells for cardiovascular diseases. Cell Death Dis. 2020; 11(5):349. PMC: 7214402. DOI: 10.1038/s41419-020-2542-9. View

13.

Worthington E, Hagood J . Therapeutic Use of Extracellular Vesicles for Acute and Chronic Lung Disease. Int J Mol Sci. 2020; 21(7). PMC: 7177288. DOI: 10.3390/ijms21072318. View

14.

Ehrlich S, Quesenberry Jr C, Van Den Eeden S, Shan J, Ferrara A . Patients diagnosed with diabetes are at increased risk for asthma, chronic obstructive pulmonary disease, pulmonary fibrosis, and pneumonia but not lung cancer. Diabetes Care. 2009; 33(1):55-60. PMC: 2797986. DOI: 10.2337/dc09-0880. View

15.

Kuznik B, Linkova N, Kolchina N, Kukanova E, Khavinson V . The JAM Family of Molecules and Their Role in the Regulation of Physiological and Pathological Processes. Usp Fiziol Nauk. 2017; 47(4):76-97. View

16.

Jeong S, An B, Han H, Kim J, Heo H, Ha K . BMP4 and perivascular cells promote hematopoietic differentiation of human pluripotent stem cells in a differentiation stage-specific manner. Exp Mol Med. 2020; 52(1):56-65. PMC: 7000736. DOI: 10.1038/s12276-019-0357-5. View

17.

Mangialardi G, Katare R, Oikawa A, Meloni M, Reni C, Emanueli C . Diabetes causes bone marrow endothelial barrier dysfunction by activation of the RhoA-Rho-associated kinase signaling pathway. Arterioscler Thromb Vasc Biol. 2013; 33(3):555-64. PMC: 3616369. DOI: 10.1161/ATVBAHA.112.300424. View

18.

Siller R, Greenhough S, Park I, Sullivan G . Modelling human disease with pluripotent stem cells. Curr Gene Ther. 2013; 13(2):99-110. PMC: 3785403. DOI: 10.2174/1566523211313020004. View

19.

Kim J, Lee J, Ha K, Han E, Park W, Min C . Perivascular Cells and NADPH Oxidase Inhibition Partially Restore Hyperglycemia-Induced Alterations in Hematopoietic Stem Cell and Myeloid-Derived Suppressor Cell Populations in the Bone Marrow. Int J Stem Cells. 2019; 12(1):63-72. PMC: 6457702. DOI: 10.15283/ijsc18097. View

20.

Pitocco D, Fuso L, Conte E, Zaccardi F, Condoluci C, Scavone G . The diabetic lung--a new target organ?. Rev Diabet Stud. 2012; 9(1):23-35. PMC: 3448171. DOI: 10.1900/RDS.2012.9.23. View