MIF/CD74 axis regulates alveolar epithelial type II cell apoptosis, autophagy, and transdifferentiation in bronchopulmonary dysplasia via the TGFβ1/SMAD4 pathway | Respiratory Research

  • Zhao ZW, Lin XX, Guo YZ, He X, Zhang XT, Huang Y. Irisin alleviates hyperoxia-induced bronchopulmonary dysplasia through activation of Nrf2/HO-1 pathway. Peptides. 2023;170:171109.

  • Sotiropoulos JX, Oei JL. The role of oxygen in the development and treatment of bronchopulmonary dysplasia. Semin Perinatol. 2023;47(6):151814.

  • Jain D, Feldman A, Sangam S. Predicting Long-Term respiratory outcomes in premature infants: is it time to move beyond bronchopulmonary dysplasia? Child (Basel). 2020;7(12):283.

  • Ala M, Mohammad Jafari R, Dehpour AR. Sildenafil beyond erectile dysfunction and pulmonary arterial hypertension: thinking about new indications. Fundam Clin Pharmacol. 2021;35:235–59.

    Google Scholar 

  • Principi N, Di Pietro GM, Esposito S. Bronchopulmonary dysplasia: clinical aspects and preventive and therapeutic strategies. J Transl Med. 2018;16:36.

    Google Scholar 

  • Choi CW, Kim BI, Hong JS, Kim EK, Kim HS, Choi JH. Bronchopulmonary dysplasia in a rat model induced by intra-amniotic inflammation and postnatal hyperoxia: morphometric aspects. Pediatr Res. 2009;65:323–7.

    Google Scholar 

  • Tang JR, Seedorf GJ, Muehlethaler V, Walker DL, Markham NE, Balasubramaniam V, et al. Moderate postnatal hyperoxia accelerates lung growth and attenuates pulmonary hypertension in infant rats after exposure to intra-amniotic endotoxin. Am J Physiol Lung Cell Mol Physiol. 2010;299:L735-748.

    Google Scholar 

  • Farr L, Ghosh S, Moonah S. Role of MIF cytokine/CD74 receptor pathway in protecting against injury and promoting repair. Front Immunol. 2020;11:1273.

    Google Scholar 

  • Marsh LM, Cakarova L, Kwapiszewska G, von Wulffen W, Herold S, Seeger W, Lohmeyer J. Surface expression of CD74 by type II alveolar epithelial cells: a potential mechanism for macrophage migration inhibitory factor-induced epithelial repair. Am J Physiol Lung Cell Mol Physiol. 2009;296:L442–452.

    Google Scholar 

  • Grieb G, Merk M, Bernhagen J, Bucala R. Macrophage migration inhibitory factor (MIF): a promising biomarker. Drug News Perspect. 2010;23:257–64.

    Google Scholar 

  • Sauler M, Leng L, Trentalange M, Haslip M, Shan P, Piecychna M, Zhang Y, Andrews N, Mannam P, Allore H, et al. Macrophage migration inhibitory factor deficiency in chronic obstructive pulmonary disease. Am J Physiol Lung Cell Mol Physiol. 2014;306:L487–496.

    Google Scholar 

  • Zhang C, Ramsey C, Berical A, Yu L, Leng L, McGinnis KA, Song Y, Michael H, McCormack MC, Allore H, et al. A functional macrophage migration inhibitory factor promoter polymorphism is associated with reduced diffusing capacity. Am J Physiol Lung Cell Mol Physiol. 2019;316:L400–5.

    Google Scholar 

  • Shi X, Leng L, Wang T, Wang W, Du X, Li J, et al. CD44 is the signaling component of the macrophage migration inhibitory factor-CD74 receptor complex. Immunity. 2006;25:595–606.

    Google Scholar 

  • Petre MA, Petrik J, Ellis R, Inman MD, Holloway AC, Labiris NR. Fetal and neonatal exposure to nicotine disrupts postnatal lung development in rats: role of VEGF and its receptors. Int J Toxicol. 2011;30:244–52.

    Google Scholar 

  • Yu S, Poe B, Schwarz M, Elliot SA, Albertine KH, Fenton S, et al. Fetal and postnatal lung defects reveal a novel and required role for Fgf8 in lung development. Dev Biol. 2010;347:92–108.

    Google Scholar 

  • Hoffman AM, Ingenito EP. Alveolar epithelial stem and progenitor cells: emerging evidence for their role in lung regeneration. Curr Med Chem. 2012;19:6003–8.

    Google Scholar 

  • Klasen C, Ziehm T, Huber M, Asare Y, Kapurniotu A, Shachar I, et al. LPS-mediated cell surface expression of CD74 promotes the proliferation of B cells in response to MIF. Cell Signal. 2018;46:32–42.

    Google Scholar 

  • Takahashi K, Koga K, Linge HM, Zhang Y, Lin X, Metz CN, et al. Macrophage CD74 contributes to MIF-induced pulmonary inflammation. Respir Res. 2009;10:33.

    Google Scholar 

  • Cao L, Wang X, Liu X, Meng W, Guo W, Duan C, et al. Tumor necrosis factor α-dependent lung inflammation promotes the progression of lung adenocarcinoma originating from alveolar type II cells by upregulating MIF-CD74. Lab Invest. 2023;103:100034.

    Google Scholar 

  • Li R, Wang F, Wei J, Lin Y, Tang G, Rao L, et al. The role of macrophage migration inhibitory factor (MIF) in asthmatic airway remodeling. Allergy Asthma Immunol Res. 2021;13:88–105.

    Google Scholar 

  • Sauler M, Zhang Y, Min JN, Leng L, Shan P, Roberts S, et al. Endothelial CD74 mediates macrophage migration inhibitory factor protection in hyperoxic lung injury. FASEB J. 2015;29:1940–9.

    Google Scholar 

  • Chen XQ, Wu SH, Luo YY, Li BJ, Li SJ, Lu HY, et al. Lipoxin A(4) attenuates bronchopulmonary dysplasia via upregulation of Let-7c and downregulation of TGF-β(1) signaling pathway. Inflammation. 2017;40:2094–108.

    Google Scholar 

  • Kunzmann S, Ottensmeier B, Speer CP, Fehrholz M. Effect of progesterone on Smad signaling and TGF-β/Smad-regulated genes in lung epithelial cells. PLoS One. 2018;13:e0200661.

    Google Scholar 

  • Jin M, Lee J, Lee KY, Jin Z, Pak JH, Kim HS. Alteration of TGF-β-ALK-Smad signaling in hyperoxia-induced bronchopulmonary dysplasia model of newborn rats. Exp Lung Res. 2016;42:354–64.

    Google Scholar 

  • Lu J, Zhong Y, Lin Z, Lin X, Chen Z, Wu X, et al. Baicalin alleviates radiation-induced epithelial-mesenchymal transition of primary type II alveolar epithelial cells via TGF-β and ERK/GSK3β signaling pathways. Biomed Pharmacother. 2017;95:1219–24.

    Google Scholar 

  • Zhou Y, Hill C, Yao L, Li J, Hancock D, Downward J, et al. Quantitative proteomic analysis in alveolar type II cells reveals the different capacities of RAS and TGF-β to induce epithelial-mesenchymal transition. Front Mol Biosci. 2021;8:595712.

    Google Scholar 

  • Bhaskaran M, Kolliputi N, Wang Y, Gou D, Chintagari NR, Liu L. Trans-differentiation of alveolar epithelial type II cells to type I cells involves autocrine signaling by transforming growth factor beta 1 through the Smad pathway. J Biol Chem. 2007;282:3968–76.

    Google Scholar 

  • Faul F, Erdfelder E, Lang AG, Buchner A. G*power 3: a flexible statistical power analysis program for the social, behavioral, and biomedical sciences. Behav Res Methods. 2007;39:175–91.

    Google Scholar 

  • Serdar CC, Cihan M, Yücel D, Serdar MA. Sample size, power and effect size revisited: simplified and practical approaches in pre-clinical, clinical and laboratory studies. Biochem Med Zagreb. 2021;31:010502.

    Google Scholar 

  • Chou HC, Li YT, Chen CM. Human mesenchymal stem cells attenuate experimental bronchopulmonary dysplasia induced by perinatal inflammation and hyperoxia. Am J Transl Res. 2016;8:342–53.

    Google Scholar 

  • Lee HJ, Kim BI, Choi ES, Choi CW, Kim EK, Kim HS, et al. Effects of postnatal dexamethasone or hydrocortisone in a rat model of antenatal lipopolysaccharide and neonatal hyperoxia exposure. J Korean Med Sci. 2012;27:395–401.

    Google Scholar 

  • Ni W, Lin N, He H, Zhu J, Zhang Y. Lipopolysaccharide induces up-regulation of TGF-α through HDAC2 in a rat model of bronchopulmonary dysplasia. PLoS One. 2014;9:e91083.

    Google Scholar 

  • Zhang Q, Ran X, He Y, Ai Q, Shi Y. Acetate downregulates the activation of NLRP3 inflammasomes and attenuates lung injury in neonatal mice with bronchopulmonary dysplasia. Front Pediatr. 2020;8:595157.

    Google Scholar 

  • Sakurai R, Lee C, Shen H, Waring AJ, Walther FJ, Rehan VK. A combination of the aerosolized PPAR-γ agonist Pioglitazone and a synthetic surfactant protein B peptide mimic prevents hyperoxia-induced neonatal lung injury in rats. Neonatology. 2018;113:296–304.

    Google Scholar 

  • Deng J, Wang SH, Zheng XM, Tang ZM. Calcitonin gene-related peptide attenuates hyperoxia-induced oxidative damage in alveolar epithelial type II cells through regulating viability and transdifferentiation. Inflammation. 2022;45:863–75.

    Google Scholar 

  • Chen XY, Kao C, Peng SW, Chang JH, Lee YL, Laiman V, Chung KF, Bhavsar PK, Heriyanto DS, Chuang KJ, Chuang HC. Role of DCLK1/Hippo pathway in type II alveolar epithelial cells differentiation in acute respiratory distress syndrome. Mol Med. 2023;29:159.

    Google Scholar 

  • Dewor M, Steffens G, Krohn R, Weber C, Baron J, Bernhagen J. Macrophage migration inhibitory factor (MIF) promotes fibroblast migration in scratch-wounded monolayers in vitro. FEBS Lett. 2007;581:4734–42.

    Google Scholar 

  • Shin HN, Moon HH, Ku JL. Stromal cell-derived factor-1α and macrophage migration-inhibitory factor induce metastatic behavior in CXCR4-expressing colon cancer cells. Int J Mol Med. 2012;30:1537–43.

    Google Scholar 

  • Cao H, Tadros V, Hiramoto B, Leeper K, Hino C, Xiao J, et al. Targeting TKI-activated NFKB2-MIF/CXCLs-CXCR2 signaling pathways in FLT3 mutated acute myeloid leukemia reduced blast viability. Biomedicines. 2022. https://doi.org/10.3390/biomedicines10051038.

    Google Scholar 

  • Poulsen KL, Fan X, Kibler CD, Huang E, Wu X, McMullen MR, Leng L, Bucala R, Ventura-Cots M, Argemi J et al. Role of MIF in coordinated expression of hepatic chemokines in patients with alcohol-associated hepatitis. JCI Insight. 2021;6(11):e141420.

  • Li X, Wang L, Hao J, Zhu Q, Guo M, Wu C, et al. The role of autophagy in lamellar body formation and surfactant production in type 2 alveolar epithelial cells. Int J Biol Sci. 2022;18:1107–19.

    Google Scholar 

  • Serralha RS, Rodrigues IF, Bertolini A, Lima DY, Nascimento M, Mouro MG, Punaro GR, Visoná I, Rodrigues AM, Higa EMS. Esculin reduces P2X7 and reverses mitochondrial dysfunction in the renal cortex of diabetic rats. Life Sci. 2020;254:117787.

    Google Scholar 

  • Zeiner PS, Preusse C, Blank AE, Zachskorn C, Baumgarten P, Caspary L, et al. MIFReceptor CD74 is Restricted to Microglia/Macrophages, Associated with a M1‐Polarized Immune Milieu and Prolonged Patient Survival in Gliomas. Brain Pathol. 2015;25(4):491–504.

    Google Scholar 

  • Zhou DN, Li SJ, Ding JL, Yin TL, Yang J, Ye H. MIF may participate in pathogenesis of polycystic ovary syndrome in rats through MAPK signalling pathway. Curr Med Sci. 2018;38(5):853–60.

    Google Scholar 

  • Huang JM, Zhao N, Hao XN, Li SY, Wei D, Pu N, et al. CX3CL1/CX3CR1 signaling mediated neuroglia activation is implicated in the retinal degeneration: a potential therapeutic target to prevent photoreceptor death. Invest Ophthalmol Vis Sci. 2024;65:29.

    Google Scholar 

  • Shen J, Ma H, Wang C. Triptolide improves myocardial fibrosis in rats through inhibition of nuclear factor kappa B and NLR family pyrin domain containing 3 inflammasome pathway. Korean J Physiol Pharmacol. 2021;25:533–43.

    Google Scholar 

  • Zhou X, Xu W, Wang Y, Zhang H, Zhang L, Li C, et al. LncRNA DNM3OS regulates GREM2 via miR-127-5p to suppress early chondrogenic differentiation of rat mesenchymal stem cells under hypoxic conditions. Cell Mol Biol Lett. 2021;26:22.

    Google Scholar 

  • Zhang D, Wu Y, Li Z, Chen H, Huang S, Jian C, et al. MiR-144-5p, an exosomal miRNA from bone marrow-derived macrophage in type 2 diabetes, impairs bone fracture healing via targeting Smad1. J Nanobiotechnol. 2021;19:226.

    Google Scholar 

  • Shang P, Liu W, Liu T, Zhang Y, Mu F, Zhu Z, et al. Acetyl-11-keto-β-boswellic acid attenuates prooxidant and profibrotic mechanisms involving transforming growth factor-β1, and improves vascular remodeling in spontaneously hypertensive rats. Sci Rep. 2016;6:39809.

    Google Scholar 

  • Wang H, Shi X, Guo Z, Zhao F, He W, Kang M, et al. Microrna-211-5p predicts the progression of postmenopausal osteoporosis and attenuates osteogenesis by targeting dual specific phosphatase 6. Bioengineered. 2022;13:5709–23.

    Google Scholar 

  • Tanguy J, Boutanquoi PM, Burgy O, Dondaine L, Beltramo G, Uyanik B, Garrido C, Bonniaud P, Bellaye PS, Goirand F. HSPB5 Inhibition by NCI-41356 reduces experimental lung fibrosis by blocking TGF-β1 signaling. Pharmaceuticals (Basel). 2023;16(2):177.

  • Shi Y, Jin Y, Liu F, Jiang J, Cao J, Lu Y, Yang J. Ceramide induces the apoptosis of non–small cell lung cancer cells through the Txnip/Trx1 complex. Int J Mol Med. 2021;47(5):85.

  • Bao T, Zhu H, Zheng Y, Hu J, Wang H, Cheng H, et al. Expression of long noncoding RNA uc.375 in bronchopulmonary dysplasia and its function in the proliferation and apoptosis of mouse alveolar epithelial cell line MLE 12. Front Physiol. 2022;13:971732.

    Google Scholar 

  • Xiong Y, Wang Q. STC1 regulates glioblastoma migration and invasion via the TGF–β/SMAD4 signaling pathway. Mol Med Rep. 2019;20:3055–64.

    Google Scholar 

  • Jiang Y, Liu Y, Xiao W, Zhang D, Liu X, Xiao H, et al. Xinmailong attenuates Doxorubicin-induced lysosomal dysfunction and oxidative stress in H9c2 cells via HO-1. Oxid Med Cell Longev. 2021;2021:5896931.

    Google Scholar 

  • Shen S, Ji C, Wei K. Cellular senescence and regulated cell death of tubular epithelial cells in diabetic kidney disease. Front Endocrinol (Lausanne). 2022;13:924299.

    Google Scholar 

  • Yu H, Li D, Zhao X, Fu J. Fetal origin of bronchopulmonary dysplasia: contribution of intrauterine inflammation. Mol Med. 2024;30:135.

    Google Scholar 

  • Parsons A, Netsanet A, Seedorf G, Abman SH, Taglauer ES. Understanding the role of placental pathophysiology in the development of bronchopulmonary dysplasia. Am J Physiol Lung Cell Mol Physiol. 2022;323:L651-8.

    Google Scholar 

  • Wei Y, Wang Y. Celastrol attenuates impairments associated with lipopolysaccharide-induced acute respiratory distress syndrome (ARDS) in rats. J Immunotoxicol. 2017;14:228–34.

    Google Scholar 

  • Roper JM, Mazzatti DJ, Watkins RH, Maniscalco WM, Keng PC, O’Reilly MA. In vivo exposure to hyperoxia induces DNA damage in a population of alveolar type II epithelial cells. Am J Physiol Lung Cell Mol Physiol. 2004;286:L1045-1054.

    Google Scholar 

  • O’Reilly MA, Staversky RJ, Finkelstein JN, Keng PC. Activation of the G2 cell cycle checkpoint enhances survival of epithelial cells exposed to hyperoxia. Am J Physiol Lung Cell Mol Physiol. 2003;284:L368-375.

    Google Scholar 

  • Sureshbabu A, Syed M, Das P, Janér C, Pryhuber G, Rahman A, et al. Inhibition of regulatory-associated protein of mechanistic target of rapamycin prevents hyperoxia-induced lung injury by enhancing autophagy and reducing apoptosis in neonatal mice. Am J Respir Cell Mol Biol. 2016;55:722–35.

    Google Scholar 

  • Chen Y, Chang L, Li W, Rong Z, Liu W, Shan R, et al. Thioredoxin protects fetal type II epithelial cells from hyperoxia-induced injury. Pediatr Pulmonol. 2010;45:1192–200.

    Google Scholar 

  • Yee M, Buczynski BW, O’Reilly MA. Neonatal hyperoxia stimulates the expansion of alveolar epithelial type II cells. Am J Respir Cell Mol Biol. 2014;50:757–66.

    Google Scholar 

  • Hou A, Fu J, Shi Y, Qiao L, Li J, Xing Y, et al. Decreased ZONAB expression promotes excessive transdifferentiation of alveolar epithelial cells in hyperoxia-induced bronchopulmonary dysplasia. Int J Mol Med. 2018;41:2339–49.

    Google Scholar 

  • Roger T, Schlapbach LJ, Schneider A, Weier M, Wellmann S, Marquis P, et al. Plasma levels of macrophage migration inhibitory factor and d-dopachrome tautomerase show a highly specific profile in early life. Front Immunol. 2017;8:26.

    Google Scholar 

  • Sun H, Choo-Wing R, Fan J, Leng L, Syed MA, Hare AA, et al. Small molecular modulation of macrophage migration inhibitory factor in the hyperoxia-induced mouse model of bronchopulmonary dysplasia. Respir Res. 2013;14:27.

    Google Scholar 

  • Prencipe G, Auriti C, Inglese R, Devito R, Ronchetti MP, Seganti G, et al. A polymorphism in the macrophage migration inhibitory factor promoter is associated with bronchopulmonary dysplasia. Pediatr Res. 2011;69:142–7.

    Google Scholar 

  • Kevill KA, Bhandari V, Kettunen M, Leng L, Fan J, Mizue Y, et al. A role for macrophage migration inhibitory factor in the neonatal respiratory distress syndrome. J Immunol. 2008;180:601–8.

    Google Scholar 

  • Gao J, Wu M, Wang F, Jiang L, Tian R, Zhu X, et al. CD74, a novel predictor for bronchopulmonary dysplasia in preterm infants. Medicine. 2020;99:e23477.

    Google Scholar 

  • Yao HC, Zhu Y, Lu HY, Ju HM, Xu SQ, Qiao Y, et al. Type 2 innate lymphoid cell-derived amphiregulin regulates type II alveolar epithelial cell transdifferentiation in a mouse model of bronchopulmonary dysplasia. Int Immunopharmacol. 2023;122:110672.

    Google Scholar 

  • Hou A, Fu J, Yang H, Zhu Y, Pan Y, Xu S, et al. Hyperoxia stimulates the transdifferentiation of type II alveolar epithelial cells in newborn rats. Am J Physiol Lung Cell Mol Physiol. 2015;308:L861-872.

    Google Scholar 

  • du Bois RM. Strategies for treating idiopathic pulmonary fibrosis. Nat Rev Drug Discov. 2010;9:129–40.

    Google Scholar 

  • Bueno M, Calyeca J, Khaliullin T, Miller MP, Alvarez D, Rosas L, Brands J, Baker C, Nasser A, Shulkowski S et al. CYB5R3 in type II alveolar epithelial cells protects against lung fibrosis by suppressing TGF-β1 signaling. JCI Insight. 2023;8(5):e161487.

  • Bueno M, Zank D, Buendia-Roldán I, Fiedler K, Mays BG, Alvarez D, et al. PINK1 attenuates MtDNA release in alveolar epithelial cells and TLR9 mediated profibrotic responses. PLoS One. 2019;14:e0218003.

    Google Scholar 

  • Chilosi M, Carloni A, Rossi A, Poletti V. Premature lung aging and cellular senescence in the pathogenesis of idiopathic pulmonary fibrosis and COPD/emphysema. Transl Res. 2013;162:156–73.

    Google Scholar 

  • Chung EJ, Kwon S, Reedy JL, White AO, Song JS, Hwang I, et al. IGF-1 receptor signaling regulates type II pneumocyte senescence and resulting macrophage polarization in lung fibrosis. Int J Radiat Oncol Biol Phys. 2021;110:526–38.

    Google Scholar 

  • Chung EJ, Reedy JL, Kwon S, Patil S, Valle L, White AO, et al. 12-lipoxygenase is a critical mediator of type II pneumocyte senescence, macrophage polarization and pulmonary fibrosis after irradiation. Radiat Res. 2019;192:367–79.

    Google Scholar 

  • Citrin DE, Shankavaram U, Horton JA, Shield W 3rd, Zhao S, Asano H, et al. Role of type II pneumocyte senescence in radiation-induced lung fibrosis. J Natl Cancer Inst. 2013;105:1474–84.

    Google Scholar 

  • Zhang T, Zhang J, Lv C, Li H, Song X. Senescent AECⅡ and the implication for idiopathic pulmonary fibrosis treatment. Front Pharmacol. 2022;13:1059434.

    Google Scholar 

  • Wójcik-Pszczoła K, Chłoń-Rzepa G, Jankowska A, Ferreira B, Koczurkiewicz-Adamczyk P, Pękala E, Wyska E, Pociecha K, Gosens R. Pan-Phosphodiesterase inhibitors attenuate TGF-β-Induced Pro-Fibrotic phenotype in alveolar epithelial type II cells by downregulating Smad-2 phosphorylation. Pharmaceuticals (Basel). 2022;15(4):423.

  • Continue Reading