Fibroblast Heterogeneity in Inflammatory Bowel Disease

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2024 Dec 17

PMID 39684719

Authors

Bo-Jun Ke

Gabriele Dragoni

Gianluca Matteoli

Affiliations

Soon will be listed here.

Abstract

Intestinal fibroblasts are pivotal players in maintaining tissue homeostasis and orchestrating responses to injury and inflammation within the gastrointestinal (GI) tract. Fibroblasts contribute significantly to the pathogenesis of inflammatory bowel disease (IBD), including Crohn's disease and ulcerative colitis (UC), by secreting pro-inflammatory cytokines, modulating immune cell activity, and promoting fibrosis. In addition, fibroblasts play crucial roles in tissue repair and regeneration following acute injury or chronic inflammation. The dysregulation of fibroblast functions can lead to fibrotic complications, such as intestinal strictures and obstruction, which are common in advanced stages of IBD. Understanding the complex interplay between fibroblasts and other cell types in the intestine is essential to elucidate the underlying mechanisms of intestinal diseases and identify novel therapeutic targets. Future research aimed at deciphering the heterogeneity of intestinal fibroblasts and their dynamic roles in disease progression holds promise for the development of precision therapies to mitigate fibrosis and inflammation in intestinal disorders.

References

Worthley D, Churchill M, Compton J, Tailor Y, Rao M, Si Y . Gremlin 1 identifies a skeletal stem cell with bone, cartilage, and reticular stromal potential. Cell. 2015; 160(1-2):269-84. PMC: 4436082. DOI: 10.1016/j.cell.2014.11.042. View

Solitano V, Dal Buono A, Gabbiadini R, Wozny M, Repici A, Spinelli A . Fibro-Stenosing Crohn's Disease: What Is New and What Is Next?. J Clin Med. 2023; 12(9). PMC: 10179180. DOI: 10.3390/jcm12093052. View

McCarthy N, Manieri E, Storm E, Saadatpour A, Luoma A, Kapoor V . Distinct Mesenchymal Cell Populations Generate the Essential Intestinal BMP Signaling Gradient. Cell Stem Cell. 2020; 26(3):391-402.e5. PMC: 7412576. DOI: 10.1016/j.stem.2020.01.008. View

Qian J, Olbrecht S, Boeckx B, Vos H, Laoui D, Etlioglu E . A pan-cancer blueprint of the heterogeneous tumor microenvironment revealed by single-cell profiling. Cell Res. 2020; 30(9):745-762. PMC: 7608385. DOI: 10.1038/s41422-020-0355-0. View

Dominici M, Le Blanc K, Mueller I, Slaper-Cortenbach I, Marini F, Krause D . Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy. 2006; 8(4):315-7. DOI: 10.1080/14653240600855905. View

Dragoni G, Ke B, Picariello L, Abdurahiman S, Ceni E, Biscu F . The Impact of Peptidyl Arginine Deiminase 4-Dependent Neutrophil Extracellular Trap Formation on the Early Development of Intestinal Fibrosis in Crohn's Disease. J Crohns Colitis. 2024; 19(1. DOI: 10.1093/ecco-jcc/jjae121. View

Antoniu S . Pirfenidone for the treatment of idiopathic pulmonary fibrosis. Expert Opin Investig Drugs. 2006; 15(7):823-8. DOI: 10.1517/13543784.15.7.823. View

Ugurlu B, Karaoz E . Comparison of similar cells: Mesenchymal stromal cells and fibroblasts. Acta Histochem. 2020; 122(8):151634. PMC: 7550172. DOI: 10.1016/j.acthis.2020.151634. View

Severi C, Sferra R, Scirocco A, Vetuschi A, Pallotta N, Pronio A . Contribution of intestinal smooth muscle to Crohn's disease fibrogenesis. Eur J Histochem. 2015; 58(4):2457. PMC: 4289851. DOI: 10.4081/ejh.2014.2457. View

10.

Abou Zahr A, Salama M, Carreau N, Tremblay D, Verstovsek S, Mesa R . Bone marrow fibrosis in myelofibrosis: pathogenesis, prognosis and targeted strategies. Haematologica. 2016; 101(6):660-71. PMC: 5013940. DOI: 10.3324/haematol.2015.141283. View

11.

Kato M, Sasaki S, Nakamura T, Kurokawa K, Yamada T, Ochi Y . Gastrointestinal adverse effects of nintedanib and the associated risk factors in patients with idiopathic pulmonary fibrosis. Sci Rep. 2019; 9(1):12062. PMC: 6700168. DOI: 10.1038/s41598-019-48593-4. View

12.

Kataria J, Kerr J, Lourenssen S, Blennerhassett M . Nintedanib regulates intestinal smooth muscle hyperplasia and phenotype in vitro and in TNBS colitis in vivo. Sci Rep. 2022; 12(1):10275. PMC: 9206006. DOI: 10.1038/s41598-022-14491-5. View

13.

Rinella M, Lieu H, Kowdley K, Goodman Z, Alkhouri N, Lawitz E . A randomized, double-blind, placebo-controlled trial of aldafermin in patients with NASH and compensated cirrhosis. Hepatology. 2023; 79(3):674-689. PMC: 10871650. DOI: 10.1097/HEP.0000000000000607. View

14.

Lefebvre V, Bhattaram P . Vertebrate skeletogenesis. Curr Top Dev Biol. 2010; 90:291-317. PMC: 3077680. DOI: 10.1016/S0070-2153(10)90008-2. View

15.

Garrido-Trigo A, Corraliza A, Veny M, Dotti I, Melon-Ardanaz E, Rill A . Macrophage and neutrophil heterogeneity at single-cell spatial resolution in human inflammatory bowel disease. Nat Commun. 2023; 14(1):4506. PMC: 10372067. DOI: 10.1038/s41467-023-40156-6. View

16.

Friedrich M, Pohin M, Jackson M, Korsunsky I, Bullers S, Rue-Albrecht K . IL-1-driven stromal-neutrophil interactions define a subset of patients with inflammatory bowel disease that does not respond to therapies. Nat Med. 2021; 27(11):1970-1981. PMC: 8604730. DOI: 10.1038/s41591-021-01520-5. View

17.

Sheng G . The developmental basis of mesenchymal stem/stromal cells (MSCs). BMC Dev Biol. 2015; 15:44. PMC: 4654913. DOI: 10.1186/s12861-015-0094-5. View

18.

Degirmenci B, Valenta T, Dimitrieva S, Hausmann G, Basler K . GLI1-expressing mesenchymal cells form the essential Wnt-secreting niche for colon stem cells. Nature. 2018; 558(7710):449-453. DOI: 10.1038/s41586-018-0190-3. View

19.

Feagan B, Sandborn W, Gasink C, Jacobstein D, Lang Y, Friedman J . Ustekinumab as Induction and Maintenance Therapy for Crohn's Disease. N Engl J Med. 2016; 375(20):1946-1960. DOI: 10.1056/NEJMoa1602773. View

20.

Wei K, Nguyen H, Brenner M . Fibroblast pathology in inflammatory diseases. J Clin Invest. 2021; 131(20). PMC: 8516469. DOI: 10.1172/JCI149538. View