APMAdvances in Precision Medicine2424-85922424-9106WHIOCE PUBLISHING PTE. LTD.10.18063/APM.v11i3.1653ArticleCurrent Status of Research Progress on Idiopathic Pulmonary Fibrosishttps://artdesignp.com/journal/APM/11/3/10.18063/APM.v11i3.1653PanXingxing,ZhouYuxin20261132026-03-26Idiopathic pulmonary fibrosis (IPF) is a chronic, irreversible interstitial lung disease characterized by diffuse pulmonary interstitial fibrosis and progressive decline in pulmonary function, with its etiology not yet fully elucidated. The pathological process primarily manifests as recurrent injury and abnormal repair of alveolar epithelial cells, sustained activation of fibroblasts, leading to excessive extracellular matrix deposition and structural remodeling of lung tissue in patients. This review focuses on the pathological features, pathogenesis, and key signaling pathways of IPF, systematically summarizing current major clinical treatment strategies to provide theoretical references for further elucidation of IPF pathogenesis and exploration of more effective prevention and therapeutic approaches.Idiopathic pulmonary fibrosis,Pulmonary fibroblasts,Pathogenesis,Signaling pathways,Anti-fibrotic therapy

[1] Podolanczuk AJ, Thomson CC, Remy-Jardin M, et al., 2023, Idiopathic Pulmonary Fibrosis: State of the Art for 2023. Eur Respir J, 61(4): 2200957. [2] Mei Q, Liu Z, Zuo H, et al., 2022, Idiopathic Pulmonary Fibrosis: An Update on Pathogenesis. Front Pharmacol, 12: 797292. [3] Ley B, Collard HR, King TE Jr., 2011, Clinical Course and Prediction of Survival in Idiopathic Pulmonary Fibrosis. Am J Respir Crit Care Med, 183(4): 431–440. [4] Maher TM, 2024, Interstitial Lung Disease: A Review. JAMA, 331(19): 1655–1665. [5] Wynn TA, 2008, Cellular and Molecular Mechanisms of Fibrosis. J Pathol, 214(2): 199–210. [6] Yu QY, Tang XX, 2022, Irreversibility of Pulmonary Fibrosis. Aging Dis, 13(1): 73–86. [7] Katzenstein AL, Myers JL, 1998, Idiopathic Pulmonary Fibrosis: Clinical Relevance of Pathological Classification. Am J Respir Crit Care Med, 157(4 Pt 1): 1301–1315. [8] Fathimath M, Shaikh SB, Jeena TM, et al., 2021, Inflammatory Mediators in Various Molecular Pathways Involved in the Development of Pulmonary Fibrosis. Int Immunopharmacol, 96: 107608. [9] Yin YQ, Peng F, Situ HJ, et al., 2022, Construction of Prediction Model of Inflammation Related Genes in Idiopathic Pulmonary Fibrosis and Its Correlation With Immune Microenvironment. Front Immunol, 13: 1010345. [10] Ge Z, Chen Y, Ma L, et al., 2024, Macrophage Polarization and Its Impact on Idiopathic Pulmonary Fibrosis. Front Immunol, 15: 1444964. [11] Raghu G, Collard HR, Egan JJ, et al., 2011, An Official ATS/ERS/JRS/ALAT Statement: Idiopathic Pulmonary Fibrosis: Evidence-Based Guidelines for Diagnosis and Management. Am J Respir Crit Care Med, 183: 788–824. [12] Zhu W, Tan C, Zhang J, 2022, Alveolar Epithelial Type 2 Cell Dysfunction in Idiopathic Pulmonary Fibrosis. Lung, 200(5): 539–547. [13] Armanios MY, Chen JJ, Cogan JD, et al., 2007, Telomerase Mutations in Families With Idiopathic Pulmonary Fibrosis. N Engl J Med, 356(13): 1317–1326. [14] Hatipoglu OF, Uctepe E, Opoku G, et al., 2021, Osteopontin Silencing Attenuates Bleomycin-Induced Murine Pulmonary Fibrosis by Regulating Epithelial-Mesenchymal Transition. Biomed Pharmacother, 139: 111633. [15] Hewlett JC, Kropski JA, Blackwell TS, 2018, Idiopathic Pulmonary Fibrosis: Epithelial-Mesenchymal Interactions and Emerging Therapeutic Targets. Matrix Biol, 71–72: 112–127. [16] Huang G, Yang X, Yu Q, et al., 2024, Overexpression of STX11 Alleviates Pulmonary Fibrosis by Inhibiting Fibroblast Activation via the PI3K/AKT/mTOR Pathway. Signal Transduct Target Ther, 9(1): 306. [17] Ma J, Sanchez-Duffhues G, Goumans MJ, et al., 2020, TGF-β-Induced Endothelial to Mesenchymal Transition in Disease and Tissue Engineering. Front Cell Dev Biol, 8: 260. [18] Sosulski ML, Gongora R, Danchuk S, et al., 2015, Deregulation of Selective Autophagy During Aging and Pulmonary Fibrosis: The Role of TGFβ1. Aging Cell, 14(5): 774–783. [19] Wang XC, Song K, Tu B, et al., 2023, New Aspects of the Epigenetic Regulation of EMT Related to Pulmonary Fibrosis. Eur J Pharmacol, 956: 175959. [20] Yu H, Liu S, Wang S, et al., 2024, The Involvement of HDAC3 in the Pathogenesis of Lung Injury and Pulmonary Fibrosis. Front Immunol, 15: 1392145. [21] Sun Z, Ji Z, Meng H, et al., 2024, Lactate Facilitated Mitochondrial Fission-Derived ROS to Promote Pulmonary Fibrosis via ERK/DRP-1 Signaling. J Transl Med, 22(1): 479. [22] Dodson M, de la Vega MR, Cholanians AB, et al., 2019, Modulating NRF2 in Disease: Timing Is Everything. Annu Rev Pharmacol Toxicol, 59: 555–575. [23] Cocconcelli E, Balestro E, Turato G, et al., 2024, Tertiary Lymphoid Structures and B-Cell Infiltration Are IPF Features with Functional Consequences. Front Immunol, 15: 1437767. [24] Gregory AD, Kliment CR, Metz HE, et al., 2015, Neutrophil Elastase Promotes Myofibroblast Differentiation in Lung Fibrosis. J Leukoc Biol, 98(2): 143–152. [25] Ren L, Chang YF, Jiang SH, et al., 2024, DNA Methylation Modification in Idiopathic Pulmonary Fibrosis. Front Cell Dev Biol, 12: 1416325. [26] Kim S, Qin Y, Park HJ, et al., 2024, MOSES: A Methylation-Based Gene Association Approach for Unveiling Environmentally Regulated Genes Linked to a Trait or Disease. Clin Epigenetics, 16(1): 161. [27] Surendran A, Huang C, Liu L, et al., 2024, Circular RNAs and Their Roles in Idiopathic Pulmonary Fibrosis. Respir Res, 25(1): 77. [28] Armanios MY, Chen JL, Cogan JD, et al., 2007, Telomerase Mutations in Families with Idiopathic Pulmonary Fibrosis. N Engl J Med, 356(13): 1317–1326. [29] Derynck R, Budi EH, 2019, Specificity, Versatility, and Control of TGF-β Family Signaling. Sci Signal, 12(570): eaav5183. [30] Derynck R, Zhang YE, 2003, Smad-Dependent and Smad-Independent Pathways in TGF-Beta Family Signalling. Nature, 425(6958): 577–584. [31] Hu HH, Chen DQ, Wang YN, et al., 2018, New Insights into TGF-β/Smad Signaling in Tissue Fibrosis. Chem Biol Interact, 292: 76–83. [32] Peng D, Fu M, Wang M, et al., 2022, Targeting TGF-β Signal Transduction for Fibrosis and Cancer Therapy. Mol Cancer, 21(1): 104. [33] Shaikh TB, Kuncha M, Andugulapati SB, et al., 2023, Dehydrozingerone Alleviates Pulmonary Fibrosis via Inhibition of Inflammation and Epithelial-Mesenchymal Transition by Regulating the Wnt/β-Catenin Pathway. Eur J Pharmacol, 953: 175820. [34] Du W, Tang Z, Yang F, et al., 2021, Icariin Attenuates Bleomycin-Induced Pulmonary Fibrosis by Targeting Hippo/YAP Pathway. Biomed Pharmacother, 143: 112152. [35] Liu J, Wang F, Luo F, 2023, The Role of JAK/STAT Pathway in Fibrotic Diseases: Molecular and Cellular Mechanisms. Biomolecules, 13(1): 119. [36] Gu S, Liang J, Zhang J, et al., 2023, Baricitinib Attenuates Bleomycin-Induced Pulmonary Fibrosis in Mice by Inhibiting TGF-β1 Signaling Pathway. Molecules, 28(5): 2195. [37] Onorati A, Havas AP, Lin B, et al., 2022, Upregulation of PD-L1 in Senescence and Aging. Mol Cell Biol, 42(10): e0017122. [38] Dong Z, Tai W, Lei W, et al., 2016, IL-27 Inhibits the TGF-β1-Induced Epithelial-Mesenchymal Transition in Alveolar Epithelial Cells. BMC Cell Biol, 17: 7. [39] Chu L, Zhuo J, Huang H, et al., 2024, Tetrandrine Alleviates Pulmonary Fibrosis by Inhibiting Alveolar Epithelial Cell Senescence through PINK1/Parkin-Mediated Mitophagy. Eur J Pharmacol, 969: 176459. [40] Liu T, Gonzalez De Los Santos F, Hirsch M, et al., 2021, Noncanonical Wnt Signaling Promotes Myofibroblast Differentiation in Pulmonary Fibrosis. Am J Respir Cell Mol Biol, 65(5): 489–499. [41] Walker NM, Mazzoni SM, Vittal R, et al., 2018, c-Jun N-Terminal Kinase (JNK)-Mediated Induction of mSin1 Expression and mTORC2 Activation in Mesenchymal Cells During Fibrosis. J Biol Chem, 293(44): 17229–17239. [42] Raghu G, Collard HR, Egan JJ, et al., 2011, An Official ATS/ERS/JRS/ALAT Statement: Idiopathic Pulmonary Fibrosis: Evidence-Based Guidelines for Diagnosis and Management. Am J Respir Crit Care Med, 183(6): 788–824. [43] Petnak T, Lertjitbanjong P, Thongprayoon C, et al., 2021, Impact of Antifibrotic Therapy on Mortality and Acute Exacerbation in Idiopathic Pulmonary Fibrosis: A Systematic Review and Meta-Analysis. Chest, 160(5): 1751–1763. [44] King TE Jr., Bradford WZ, Castro-Bernardini S, et al., 2014, A Phase 3 Trial of Pirfenidone in Patients with Idiopathic Pulmonary Fibrosis. N Engl J Med, 370(22): 2083–2092. [45] Richeldi L, du Bois RM, Raghu G, et al., 2014, Nintedanib in Idiopathic Pulmonary Fibrosis. N Engl J Med, 370(22): 2071–2082. [46] Kolb M, Egan JJ, Grossman J, et al., 2015, Official ATS/ERS/JRS/ALAT Clinical Practice Guideline: Management of Idiopathic Pulmonary Fibrosis. Am J Respir Crit Care Med, 192(2): e20–e40. [47] Yusen RD, Edwards LB, Christie JD, et al., 2017, The Registry of the International Society for Heart and Lung Transplantation: 34th Official Adult Lung and Heart-Lung Transplant Report--2017; Focus Theme: Allograft Ischemic Time. J Heart Lung Transplant, 36(10): 1089–1103.