细胞衰老与瘢痕纤维化的关系研究进展

doi:10.3969/j.issn.1006-5725.2024.12.023

Abstract

Abstract:

Cellular senescence and fibrosis are two biological processes that are closely related to the development of many diseases. Cellular senescence can occur through mechanisms such as telomere shortening， DNA damage， and oxidative stress， leading to degradation of cell function and decreased ability to repair damage. More and more studies have shown that fibrosis and cell senescence are closely related， and cell senescence has been confirmed to be involved in the occurrence and development of scar fibrosis diseases. An in-depth understanding of the relationship between cellular senescence and scar fibrosis is helpful to find new therapeutic strategies and develop targeted drugs to reduce the process of scar fibrosis.

Key words: cellular senescence, fibrosis of scar, targeted therapy

CLC Number:

R361+.3

Jingwen AN,Junyun FENG,Lei RAO,Dewu LIU. Research progress on relationship between cellular senescence and scar fibrosis[J]. The Journal of Practical Medicine, 2024, 40(12): 1749-1754.

References 46

1	MORETTI L， STALFORT J， BARKER T H， et al. The interplay of fibroblasts， the extracellular matrix， and inflammation in scar formation ［J］. J Biol Chem， 2022， 298（2）： 101530. doi:10.1016/j.jbc.2021.101530 doi: 10.1016/j.jbc.2021.101530
2	DI MICCO R， KRIZHANOVSKY V， BAKER D， et al. Cellular senescence in ageing： from mechanisms to therapeutic opportunities ［J］. Nat Rev Mol Cell Biol， 2021， 22（2）： 75-95. doi:10.1038/s41580-020-00314-w doi: 10.1038/s41580-020-00314-w
3	GIRE V， DULIC V. Senescence from G2 arrest， revisited ［J］. Cell Cycle， 2015， 14（3）： 297-304. doi:10.1080/15384101.2014.1000134 doi: 10.1080/15384101.2014.1000134
4	KUILMAN T， MICHALOGLOU C， MOOI W J， et al. The essence of senescence ［J］. Genes Dev， 2010， 24（22）： 2463-2479. doi:10.1101/gad.1971610 doi: 10.1101/gad.1971610
5	SCHUSTER R， YOUNESI F， EZZO M， et al. The Role of Myofibroblasts in Physiological and Pathological Tissue Repair ［J］. Cold Spring Harb Perspect Biol， 2023， 15（1）： a041231. doi:10.1101/cshperspect.a041231 doi: 10.1101/cshperspect.a041231
6	ZHANG L， PITCHER L E， YOUSEFZADEH M J， et al. Cellular senescence： a key therapeutic target in aging and diseases ［J］. J Clin Invest， 2022， 132（15）： e158450. doi:10.1172/jci158450 doi: 10.1172/jci158450
7	BIRCH J， GIL J. Senescence and the SASP： many therapeutic avenues ［J］. Genes Dev， 2020， 34（23-24）： 1565-1576. doi:10.1101/gad.343129.120 doi: 10.1101/gad.343129.120
8	KUMARI R， JAT P. Mechanisms of Cellular Senescence： Cell Cycle Arrest and Senescence Associated Secretory Phenotype ［J］. Front Cell Dev Biol， 2021， 9：645593. doi:10.3389/fcell.2021.645593 doi: 10.3389/fcell.2021.645593
9	PETROVA N V， VELICHKO A K， RAZIN S V， et al. Small molecule compounds that induce cellular senescence ［J］. Aging Cell， 2016， 15（6）： 999-1017. doi:10.1111/acel.12518 doi: 10.1111/acel.12518
10	HUANG W， HICKSON L J， EIRIN A， et al. Cellular senescence： the good， the bad and the unknown ［J］. Nat Rev Nephrol， 2022， 18（10）： 611-627. doi:10.1038/s41581-022-00601-z doi: 10.1038/s41581-022-00601-z
11	BASISTY N， KALE A， JEON O H， et al. A proteomic atlas of senescence-associated secretomes for aging biomarker development ［J］. PLoS Biol， 2020， 18（1）： e3000599. doi:10.1371/journal.pbio.3000599 doi: 10.1371/journal.pbio.3000599
12	HENDERSON N C， RIEDER F， WYNN T A. Fibrosis： from mechanisms to medicines ［J］. Nature， 2020， 587（7835）： 555-566. doi:10.1038/s41586-020-2938-9 doi: 10.1038/s41586-020-2938-9
13	ZHOU D， BORSA M， SIMON A K. Hallmarks and detection techniques of cellular senescence and cellular ageing in immune cells ［J］. Aging Cell， 2021， 20（2）： e13316. doi:10.1111/acel.13316 doi: 10.1111/acel.13316
14	CUOLLO L， ANTONANGELI F， SANTONI A， et al. The Senescence-Associated Secretory Phenotype （SASP） in the Challenging Future of Cancer Therapy and Age-Related Diseases ［J］. Biology （Basel）， 2020， 9（12）： 485. doi:10.3390/biology9120485 doi: 10.3390/biology9120485
15	YOUNIS L T， HASSAN M I ABU， TAIYEB ALI T B， et al. 3D TECA hydrogel reduces cellular senescence and enhances fibroblasts migration in wound healing ［J］. Asian J Pharm Sci， 2018， 13（4）： 317-325. doi:10.1016/j.ajps.2017.12.003 doi: 10.1016/j.ajps.2017.12.003
16	BANG M， RYU O， KIM D G， et al. Tenovin-1 Induces Senescence and Decreases Wound-Healing Activity in Cultured Rat Primary Astrocytes ［J］. Biomol Ther （Seoul）， 2019， 27（3）： 283-289. doi:10.4062/biomolther.2018.107 doi: 10.4062/biomolther.2018.107
17	BLOKLAND K E C， WATERS D W， SCHULIGA M， et al. Senescence of IPF Lung Fibroblasts Disrupt Alveolar Epithelial Cell Proliferation and Promote Migration in Wound Healing ［J］. Pharmaceutics， 2020， 12（4）： 389. doi:10.3390/pharmaceutics12040389 doi: 10.3390/pharmaceutics12040389
18	XU M， SU X， XIAO X， et al. Hydrogen Peroxide-Induced Senescence Reduces the Wound Healing-Promoting Effects of Mesenchymal Stem Cell-Derived Exosomes Partially via miR-146a ［J］. Aging Dis， 2021， 12（1）： 102-115. doi:10.14336/ad.2020.0624 doi: 10.14336/ad.2020.0624
19	WILKINSON H N， CLOWES C， BANYARD K L， et al. Elevated Local Senescence in Diabetic Wound Healing Is Linked to Pathological Repair via CXCR2 ［J］. J Invest Dermatol， 2019， 139（5）： 1171-1181.e6. doi:10.1016/j.jid.2019.01.005 doi: 10.1016/j.jid.2019.01.005
20	MOHAMAD KAMAL N S， SAFUAN S， SHAMSUDDIN S， et al. Aging of the cells： Insight into cellular senescence and detection Methods ［J］. Eur J Cell Biol， 2020， 99（6）： 151108. doi:10.1016/j.ejcb.2020.151108 doi: 10.1016/j.ejcb.2020.151108
21	JUN J I， LAU L F. The matricellular protein CCN1 induces fibroblast senescence and restricts fibrosis in cutaneous wound healing ［J］. Nat Cell Biol， 2010， 12（7）： 676-685. doi:10.1038/ncb2070 doi: 10.1038/ncb2070
22	冷敏，彭颖，林晓莹，等. 自噬在创面愈合中的作用研究进展［J］. 实用医学杂志， 2020， 36（22）： 3157-3160+3165. doi:10.3969/j.issn.1006-5725.2020.22.026 doi: 10.3969/j.issn.1006-5725.2020.22.026
23	WILKINSON H N， HARDMAN M J. Cellular Senescence in Acute and Chronic Wound Repair ［J］. Cold Spring Harb Perspect Biol， 2022， 14（11）： a041221.
24	SCHAFER M J， WHITE T A， IIJIMA K， et al. Cellular senescence mediates fibrotic pulmonary disease ［J］. Nat Commun， 2017， 8：14532. doi:10.1093/geroni/igx004.547 doi: 10.1093/geroni/igx004.547
25	LIU R M， LIU G. Cell senescence and fibrotic lung diseases ［J］. Exp Gerontol， 2020， 132：110836. doi:10.1016/j.exger.2020.110836 doi: 10.1016/j.exger.2020.110836
26	YAO C， GUAN X， CARRARO G， et al. Senescence of Alveolar Type 2 Cells Drives Progressive Pulmonary Fibrosis ［J］. Am J Respir Crit Care Med， 2021， 203（6）： 707-717. doi:10.1164/rccm.202004-1274oc doi: 10.1164/rccm.202004-1274oc
27	LUCAS J H， WANG Q， MUTHUMALAGE T， et al. Multi-Walled Carbon Nanotubes （MWCNTs） Cause Cellular Senescence in TGF-β Stimulated Lung Epithelial Cells ［J］. Toxics， 2021， 9（6）： 144. doi:10.3390/toxics9060144 doi: 10.3390/toxics9060144
28	RACKOW A R， NAGEL D J， MCCARTHY C， et al. The self-fulfilling prophecy of pulmonary fibrosis： a selective inspection of pathological signalling loops ［J］. Eur Respir J， 2020， 56（5）： 2000075. doi:10.1183/13993003.00075-2020 doi: 10.1183/13993003.00075-2020
29	HERNANDEZ-GONZALEZ F， FANER R， ROJAS M， et al. Cellular Senescence in Lung Fibrosis ［J］. Int J Mol Sci， 2021， 22（13）： 7012. doi:10.3390/ijms22137012 doi: 10.3390/ijms22137012
30	ÁLVAREZ D， CÁRDENES N， SELLARÉS J， et al. IPF lung fibroblasts have a senescent phenotype ［J］. Am J Physiol Lung Cell Mol Physiol， 2017， 313（6）： L1164-L1173. doi:10.1152/ajplung.00220.2017 doi: 10.1152/ajplung.00220.2017
31	PARIMON T， HOHMANN M S， YAO C. Cellular Senescence： Pathogenic Mechanisms in Lung Fibrosis ［J］. Int J Mol Sci， 2021， 22（12）： 6214. doi:10.3390/ijms22126214 doi: 10.3390/ijms22126214
32	XU J， ZHOU L， LIU Y. Cellular Senescence in Kidney Fibrosis： Pathologic Significance and Therapeutic Strategies ［J］. Front Pharmacol， 2020， 11：601325. doi:10.3389/fphar.2020.601325 doi: 10.3389/fphar.2020.601325
33	ZHANG J Q， LI Y Y， ZHANG X Y， et al. Cellular senescence of renal tubular epithelial cells in renal fibrosis ［J］. Front Endocrinol （Lausanne）， 2023， 14：1085605. doi:10.3389/fendo.2023.1085605 doi: 10.3389/fendo.2023.1085605
34	LIN C H， CHEN J， ZHANG Z， et al. Endostatin and transglutaminase 2 are involved in fibrosis of the aging kidney ［J］. Kidney Int， 2016， 89（6）： 1281-1292. doi:10.1016/j.kint.2016.01.030 doi: 10.1016/j.kint.2016.01.030
35	LUO C， ZHOU S， ZHOU Z， et al. Wnt9a Promotes Renal Fibrosis by Accelerating Cellular Senescence in Tubular Epithelial Cells ［J］. J Am Soc Nephrol， 2018， 29（4）： 1238-1256. doi:10.1681/asn.2017050574 doi: 10.1681/asn.2017050574
36	ZHANG M， SERNA-SALAS S， DAMBA T， et al. Hepatic stellate cell senescence in liver fibrosis： Characteristics， mechanisms and perspectives ［J］. Mech Ageing Dev， 2021， 199：111572. doi:10.1016/j.mad.2021.111572 doi: 10.1016/j.mad.2021.111572
37	SUGIHARA H， TERAMOTO N， YAMANOUCHI K， et al. Oxidative stress-mediated senescence in mesenchymal progenitor cells causes the loss of their fibro/adipogenic potential and abrogates myoblast fusion ［J］. Aging （Albany NY）， 2018， 10（4）： 747-763. doi:10.18632/aging.101425 doi: 10.18632/aging.101425
38	KONG X， FENG D， WANG H， et al. Interleukin-22 induces hepatic stellate cell senescence and restricts liver fibrosis in mice ［J］. Hepatology， 2012， 56（3）： 1150-1159. doi:10.1002/hep.25744 doi: 10.1002/hep.25744
39	WAN Y， MENG F， WU N， et al. Substance P increases liver fibrosis by differential changes in senescence of cholangiocytes and hepatic stellate cells ［J］. Hepatology， 2017， 66（2）： 528-541. doi:10.1002/hep.29138 doi: 10.1002/hep.29138
40	BANALES J M， MARIN J J G， LAMARCA A， et al. Cholangiocarcinoma 2020： the next horizon in mechanisms and management ［J］. Nat Rev Gastroenterol Hepatol， 2020， 17（9）： 557-588. doi:10.1038/s41575-020-0310-z doi: 10.1038/s41575-020-0310-z
41	LAGOUMTZI S M， CHONDROGIANNI N. Senolytics and senomorphics： Natural and synthetic therapeutics in the treatment of aging and chronic diseases ［J］. Free Radic Biol Med， 2021， 171：169-190. doi:10.1016/j.freeradbiomed.2021.05.003 doi: 10.1016/j.freeradbiomed.2021.05.003
42	JUSTICE J N， NAMBIAR A M， TCHKONIA T， et al. Senolytics in idiopathic pulmonary fibrosis： Results from a first-in-human， open-label， pilot study ［J］. E Bio Medicine， 2019， 40：554-563. doi:10.1016/j.ebiom.2018.12.052 doi: 10.1016/j.ebiom.2018.12.052
43	DONG D， CAI G Y， NING Y C， et al. Alleviation of senescence and epithelial-mesenchymal transition in aging kidney by short-term caloric restriction and caloric restriction mimetics via modulation of AMPK/mTOR signaling ［J］. Oncotarget， 2017， 8（10）： 16109-16121. doi:10.18632/oncotarget.14884 doi: 10.18632/oncotarget.14884
44	SELVARANI R， MOHAMMED S， RICHARDSON A. Effect of rapamycin on aging and age-related diseases-past and future ［J］. Geroscience， 2021， 43（3）： 1135-1158. doi:10.1007/s11357-020-00274-1 doi: 10.1007/s11357-020-00274-1
45	YANG H， CHEN C， CHEN H， et al. Navitoclax （ABT263） reduces inflammation and promotes chondrogenic phenotype by clearing senescent osteoarthritic chondrocytes in osteoarthritis ［J］. Aging （Albany NY）， 2020， 12（13）： 12750-12770. doi:10.18632/aging.103177 doi: 10.18632/aging.103177
46	杨胜红，欧应勇，欧阳瑶. IL-17A及PI3K/Akt/mTOR信号通路在气道重塑中的研究进展［J］. 实用医学杂志， 2022， 38（1）： 116-119. doi:10.3969/j.issn.1006-5725.2022.01.022 doi: 10.3969/j.issn.1006-5725.2022.01.022

[1]	Hui FANG,Yiting YUAN,Yongchun ZHANG,Shanshan REN,Lulu CHEN,Wei LIAO,Ai. TIAN. Regulation of PU.1 on apoptosis resistance of aging macrophages stimulated by Porphyromonas gingivalis lipopolysaccharide [J]. The Journal of Practical Medicine, 2025, 41(4): 471-477.
[2]	Kui XU,Jun. ZHOU. Research progress of ultrasound microbubbles in diagnosis and treatment of thyroid cancer [J]. The Journal of Practical Medicine, 2025, 41(3): 454-458.
[3]	Xingyu WAN,Nan LI,Shuiqing LIU,Xi. ZHANG. Research advances of mesenchymal stem cells in the bone marrow microenvironment of acute myeloid leukemia [J]. The Journal of Practical Medicine, 2025, 41(2): 294-299.
[4]	Fazhu FEI,Jiajun LU,Shuai ZHANG,Hao LI,Bin REN. Clinical application progress of immunization and targeted therapy for Hepatocellular Carcinoma in special populations [J]. The Journal of Practical Medicine, 2024, 40(6): 738-742.
[5]	Ji JIN,Hong SUN,Yong ZHUANG,Xu NING,Miao LIU. Research progress on mechanism and treatment of intervertebral disc aging [J]. The Journal of Practical Medicine, 2024, 40(22): 3268-3274.
[6]	Sishi XU,Peipei. YE. Clinical research progress of BTK inhibitors in the treatment of mantle cell lymphoma [J]. The Journal of Practical Medicine, 2024, 40(17): 2363-2368.
[7]	Yuting LI,Qilu YAN,Qibin. SONG. Molecular basis of variability in EGFR⁃targeted therapy response in non⁃small cell lung cancer [J]. The Journal of Practical Medicine, 2024, 40(15): 2166-2171.
[8]	LIU Yi, PEI Renzhi.. Advances of BCL ⁃ 2 inhibitor Venetoclaxfor higher ⁃ risk groups of myelodysplastic syndromes [J]. The Journal of Practical Medicine, 2022, 38(16): 2106-2109.
[9]	NIU Chunyan, SHI Yongqiang, CHEN Yue.. Targeted therapeutic drugs for nonalcoholic fatty liver disease：A review of literature [J]. The Journal of Practical Medicine, 2022, 38(11): 1439-1442.
[10]	LI Depei, CHEN Zhongping.. Current statue and advances of treatment for gliomas [J]. The Journal of Practical Medicine, 2021, 37(18): 2312-2316.

Research progress on relationship between cellular senescence and scar fibrosis

RichHTML

PDF (PC)

Knowledge

Abstract

Cite this article

share this article

References 46

Related Articles 10

Recommended Articles

Metrics

Comments