دورية أكاديمية
أعرض في EDS

Preadipocytes in human granulation tissue: role in wound healing and response to macrophage polarization.

التفاصيل البيبلوغرافية
العنوان: Preadipocytes in human granulation tissue: role in wound healing and response to macrophage polarization.
المؤلفون: Rauchenwald T; Department of Plastic, Reconstructive and Aesthetic Surgery, Medical University of Innsbruck, Innsbruck, Austria., Handle F; Institute of Pathology, Neuropathology and Molecular Pathology, Medical University Innsbruck, Innsbruck, Austria., Connolly CE; Department of Plastic, Reconstructive and Aesthetic Surgery, Medical University of Innsbruck, Innsbruck, Austria., Degen A; Department of Plastic, Reconstructive and Aesthetic Surgery, Medical University of Innsbruck, Innsbruck, Austria., Seifarth C; Institute of Clinical and Functional Anatomy, Medical University of Innsbruck, Innsbruck, Austria., Hermann M; Department of Anesthesiology and Critical Care Medicine, Medical University of Innsbruck, Innsbruck, Austria., Tripp CH; Department of Dermatology, Venereology and Allergology, Medical University of Innsbruck, Innsbruck, Austria., Wilflingseder D; Institute of Hygiene and Medical Microbiology, Medical University of Innsbruck, Innsbruck, Austria., Lobenwein S; Department of Plastic, Reconstructive and Aesthetic Surgery, Medical University of Innsbruck, Innsbruck, Austria., Savic D; Department of Therapeutic Radiology and Oncology, Medical University of Innsbruck, EXTRO-Lab, Tyrolean Cancer Research Institute, Innsbruck, Austria., Pölzl L; Department of Cardiac Surgery, Medical University of Innsbruck, Innsbruck, Austria., Morandi EM; Department of Plastic, Reconstructive and Aesthetic Surgery, Medical University of Innsbruck, Innsbruck, Austria., Wolfram D; Department of Plastic, Reconstructive and Aesthetic Surgery, Medical University of Innsbruck, Innsbruck, Austria., Skvortsova II; Department of Therapeutic Radiology and Oncology, Medical University of Innsbruck, EXTRO-Lab, Tyrolean Cancer Research Institute, Innsbruck, Austria., Stoitzner P; Department of Dermatology, Venereology and Allergology, Medical University of Innsbruck, Innsbruck, Austria., Haybaeck J; Institute of Pathology, Neuropathology and Molecular Pathology, Medical University Innsbruck, Innsbruck, Austria.; Diagnostic and Research Center for Molecular Biomedicine, Institute of Pathology, Medical University of Graz, Graz, Austria., Konschake M; Institute of Clinical and Functional Anatomy, Medical University of Innsbruck, Innsbruck, Austria., Pierer G; Department of Plastic, Reconstructive and Aesthetic Surgery, Medical University of Innsbruck, Innsbruck, Austria., Ploner C; Department of Plastic, Reconstructive and Aesthetic Surgery, Medical University of Innsbruck, Innsbruck, Austria. christian.ploner@i-med.ac.at.
المصدر: Inflammation and regeneration [Inflamm Regen] 2023 Oct 31; Vol. 43 (1), pp. 53. Date of Electronic Publication: 2023 Oct 31.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: BioMed Central Country of Publication: England NLM ID: 101479577 Publication Model: Electronic Cited Medium: Print ISSN: 1880-9693 (Print) Linking ISSN: 18808190 NLM ISO Abbreviation: Inflamm Regen Subsets: PubMed not MEDLINE
أسماء مطبوعة: Publication: 2016- : London : BioMed Central
Original Publication: Kawasaki-shi : Nihon Enshō Saiseo Igakkai
مستخلص: Background: Chronic non-healing wounds pose a global health challenge. Under optimized conditions, skin wounds heal by the formation of scar tissue. However, deregulated cell activation leads to persistent inflammation and the formation of granulation tissue, a type of premature scar tissue without epithelialization. Regenerative cells from the wound periphery contribute to the healing process, but little is known about their cellular fate in an inflammatory, macrophage-dominated wound microenvironment.
Methods: We examined CD45 - /CD31 - /CD34 + preadipocytes and CD68 + macrophages in human granulation tissue from pressure ulcers (n=6) using immunofluorescence, immunohistochemistry, and flow cytometry. In vitro, we studied macrophage-preadipocyte interactions using primary human adipose-derived stem cells (ASCs) exposed to conditioned medium harvested from IFNG/LPS (M1)- or IL4/IL13 (M2)-activated macrophages. Macrophages were derived from THP1 cells or CD14 + monocytes. In addition to confocal microscopy and flow cytometry, ASCs were analyzed for metabolic (OXPHOS, glycolysis), morphological (cytoskeleton), and mitochondrial (ATP production, membrane potential) changes. Angiogenic properties of ASCs were determined by HUVEC-based angiogenesis assay. Protein and mRNA levels were assessed by immunoblotting and quantitative RT-PCR.
Results: CD45 - /CD31 - /CD34 + preadipocytes were observed with a prevalence of up to 1.5% of total viable cells in human granulation tissue. Immunofluorescence staining suggested a spatial proximity of these cells to CD68 + macrophages in vivo. In vitro, ASCs exposed to M1, but not to M2 macrophage secretome showed a pro-fibrotic response characterized by stress fiber formation, elevated alpha smooth muscle actin (SMA), and increased expression of integrins ITGA5 and ITGAV. Macrophage-secreted IL1B and TGFB1 mediated this response via the PI3K/AKT and p38-MAPK pathways. In addition, ASCs exposed to M1-inflammatory stress demonstrated reduced migration, switched to a glycolysis-dominated metabolism with reduced ATP production, and increased levels of inflammatory cytokines such as IL1B, IL8, and MCP1. Notably, M1 but not M2 macrophages enhanced the angiogenic potential of ASCs.
Conclusion: Preadipocyte fate in wound tissue is influenced by macrophage polarization. Pro-inflammatory M1 macrophages induce a pro-fibrotic response in ASCs through IL1B and TGFB1 signaling, while anti-inflammatory M2 macrophages have limited effects. These findings shed light on cellular interactions in chronic wounds and provide important information for the potential therapeutic use of ASCs in human wound healing.
(© 2023. The Author(s).)
References: PLoS One. 2014 Apr 09;9(4):e94496. (PMID: 24718556)
Trends Mol Med. 2009 Aug;15(8):369-79. (PMID: 19665431)
Front Physiol. 2018 May 01;9:419. (PMID: 29765329)
Scand J Immunol. 2008 May;67(5):453-63. (PMID: 18405323)
Nature. 2017 May 11;545(7653):224-228. (PMID: 28467822)
Mol Endocrinol. 2009 Jan;23(1):11-24. (PMID: 18945811)
Wound Repair Regen. 2016 Jul;24(4):613-29. (PMID: 27196106)
Carcinogenesis. 2005 Oct;26(10):1657-67. (PMID: 15905207)
PLoS One. 2014 Aug 05;9(8):e103982. (PMID: 25093816)
Chem Biol Drug Des. 2021 Mar;97(3):774-794. (PMID: 33191630)
Annu Rev Pathol. 2010;5:99-118. (PMID: 20078217)
Molecules. 2021 Aug 13;26(16):. (PMID: 34443506)
Adv Wound Care (New Rochelle). 2018 Jul 1;7(7):209-231. (PMID: 29984112)
J Pathol. 2015 Aug;236(4):433-44. (PMID: 25875529)
Nat Commun. 2022 Jan 10;13(1):181. (PMID: 35013299)
J Clin Invest. 2011 Mar;121(3):985-97. (PMID: 21317534)
Nat Rev Cancer. 2021 Mar;21(3):162-180. (PMID: 33462499)
Mol Cell. 2022 Apr 7;82(7):1261-1277.e9. (PMID: 35305311)
Physiol Rev. 2019 Jan 1;99(1):665-706. (PMID: 30475656)
J Exp Med. 2011 Feb 14;208(2):313-26. (PMID: 21242296)
Front Immunol. 2021 Jun 16;12:681710. (PMID: 34220830)
Obesity (Silver Spring). 2007 Dec;15(12):2925-31. (PMID: 18198300)
Nat Commun. 2017 Oct 16;8(1):949. (PMID: 29038421)
Cell Mol Life Sci. 2013 Jun;70(12):2059-81. (PMID: 23052205)
JID Innov. 2022 Jun 02;2(5):100138. (PMID: 36017415)
J Immunol. 2010 Apr 1;184(7):3964-77. (PMID: 20176743)
Biomolecules. 2021 May 08;11(5):. (PMID: 34066746)
Eur Surg Res. 2017;58(1-2):81-94. (PMID: 27974711)
Circ Res. 1998 Aug 24;83(4):345-52. (PMID: 9721691)
Sci Rep. 2020 Jul 14;10(1):11568. (PMID: 32665552)
Nat Rev Immunol. 2011 Oct 14;11(11):723-37. (PMID: 21997792)
Development. 2013 Apr;140(7):1517-27. (PMID: 23482487)
PLoS One. 2010 Mar 04;5(3):e9539. (PMID: 20209061)
Cell Stem Cell. 2020 Jun 4;26(6):880-895.e6. (PMID: 32302523)
Am J Physiol Lung Cell Mol Physiol. 2000 Feb;278(2):L407-16. (PMID: 10666126)
Biochim Biophys Acta. 2011 Sep;1813(9):1619-33. (PMID: 21167873)
Stem Cell Res Ther. 2021 May 10;12(1):280. (PMID: 33971957)
Cell. 2008 Jun 13;133(6):1019-31. (PMID: 18555778)
J Invest Dermatol. 2018 Apr;138(4):811-825. (PMID: 29391249)
Cell Death Dis. 2015 Jan 15;6:e1597. (PMID: 25590807)
Int J Low Extrem Wounds. 2023 Sep;22(3):524-530. (PMID: 34180745)
Sci Rep. 2016 Jul 01;6:28889. (PMID: 27363302)
J Cell Biol. 2007 Dec 3;179(5):1043-57. (PMID: 18056416)
Methods Mol Biol. 2021;2299:17-47. (PMID: 34028733)
Methods Enzymol. 2014;547:309-54. (PMID: 25416364)
Cell. 2017 Apr 20;169(3):381-405. (PMID: 28431241)
J Invest Dermatol. 1998 Nov;111(5):850-7. (PMID: 9804349)
Int J Mol Sci. 2018 May 08;19(5):. (PMID: 29738484)
Curr Opin Cell Biol. 2007 Oct;19(5):557-64. (PMID: 17942298)
Front Pharmacol. 2020 Mar 03;11:158. (PMID: 32194404)
Int J Mol Sci. 2017 Jul 17;18(7):. (PMID: 28714933)
Adv Ther. 2017 Mar;34(3):599-610. (PMID: 28108895)
Adv Wound Care (New Rochelle). 2013 Sep;2(7):379-388. (PMID: 24527354)
Nature. 2006 Nov 30;444(7119):633-7. (PMID: 17136093)
An Bras Dermatol. 2016 Sep-Oct;91(5):614-620. (PMID: 27828635)
Proc Natl Acad Sci U S A. 1985 Mar;82(6):1589-93. (PMID: 2858849)
Mol Biol Cell. 2017 Oct 1;28(20):2661-2675. (PMID: 28768826)
EMBO J. 2020 Oct 1;39(19):e104743. (PMID: 32779739)
J Leukoc Biol. 2011 Apr;89(4):557-63. (PMID: 21248152)
J Exp Biol. 2003 Jun;206(Pt 12):2049-57. (PMID: 12756287)
Nucleic Acids Res. 1989 Mar 25;17(6):2366. (PMID: 2539586)
J Invest Dermatol. 2019 May;139(5):1171-1181.e6. (PMID: 30684552)
J Biol Chem. 2013 Aug 16;288(33):23798-806. (PMID: 23836898)
Nature. 2013 Dec 12;504(7479):277-281. (PMID: 24336287)
Histol Histopathol. 2017 Apr;32(4):351-360. (PMID: 27363977)
Front Immunol. 2014 Oct 17;5:514. (PMID: 25368618)
J Hepatol. 2005 Mar;42(3):358-64. (PMID: 15710218)
Science. 2015 Apr 17;348(6232):aaa2151. (PMID: 25883361)
Curr Protoc Toxicol. 2014 May 27;60:25.2.1-16. (PMID: 24865646)
Trends Microbiol. 2018 Feb;26(2):158-168. (PMID: 28823569)
Nature. 2019 Oct;574(7779):553-558. (PMID: 31645721)
Cell Death Differ. 2015 Feb;22(2):248-57. (PMID: 25323588)
Curr Opin Endocr Metab Res. 2021 Feb;16:102-112. (PMID: 33748531)
Dev Cell. 2005 Sep;9(3):389-402. (PMID: 16139227)
Plast Reconstr Surg. 2016 Sep;138(3 Suppl):18S-28S. (PMID: 27556760)
Science. 2018 Nov 23;362(6417):. (PMID: 30467144)
فهرسة مساهمة: Keywords: Adipose-derived stem cells; Granulation tissue; Inflammation; Macrophage polarization; Myofibroblasts; Preadipocytes; Tissue fibrosis; Wound healing
تواريخ الأحداث: Date Created: 20231031 Latest Revision: 20231102
رمز التحديث: 20240628
مُعرف محوري في PubMed: PMC10617061
DOI: 10.1186/s41232-023-00302-5
PMID: 37904253
قاعدة البيانات: MEDLINE
الوصف
تدمد:1880-9693
DOI:10.1186/s41232-023-00302-5