Induction of fibroblast-to-myofibroblast differentiation by alteration of cytoplasmic actin ratio
- Authors: Levuschkina Y.G.1, Dugina V.B.1, Shagieva G.S.1, Boichuk S.V.2,3, Eremin I.I.4, Khromova N.V.5, Kopnin P.B.5
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Affiliations:
- Lomonosov Moscow State University
- Kazan State Medical University
- Russian Medical Academy of Continuous Professional Education
- Petrovsky National Research Center of Surgery
- N. N. Blokhin National Medical Research Center of Oncology
- Issue: Vol 90, No 2 (2025)
- Pages: 321-331
- Section: Articles
- URL: https://journal-vniispk.ru/0320-9725/article/view/291908
- DOI: https://doi.org/10.31857/S0320972525020112
- EDN: https://elibrary.ru/BKPPBI
- ID: 291908
Cite item
Abstract
Myofibroblasts, which play a crucial role in the tumour microenvironment, represent a promising avenue for research in the field of oncotherapy. This study investigates the potential for induced differentiation of human fibroblasts into myofibroblasts through the downregulation of the γ-cytoplasmic actin (γ-CYA), which was achieved by RNA interference. A decrease in γ-CYA expression in human subcutaneous fibroblasts resulted in the upregulation of myofibroblast markers, including α-smooth muscle actin (α-SMA), ED-A FN, and type III collagen. These changes were accompanied by notable alterations in cellular morphology, characterised by a significant increase in cell area and formation of pronounced supermature focal adhesions. The downregulation of γ-CYA resulted in a compensatory increase in the expression of β-cytoplasmic actin and α-SMA, and the formation of characteristic α-SMA-positive stress fibers. In conclusion, our results demonstrate that a reduction in γ-CYA expression leads to myofibroblastic trans-differentiation of human subcutaneous fibroblasts.
About the authors
Y. G. Levuschkina
Lomonosov Moscow State University; Lomonosov Moscow State University
Email: pbkopnin@mail.ru
Belozersky Institute of Physico-Chemical Biology, Faculty of Biology
Russian Federation, 119992 Moscow; 119991 MoscowV. B. Dugina
Lomonosov Moscow State University; Lomonosov Moscow State University
Email: pbkopnin@mail.ru
Belozersky Institute of Physico-Chemical Biology, Faculty of Biology
Russian Federation, 119992 Moscow; 119991 MoscowG. S. Shagieva
Lomonosov Moscow State University
Email: pbkopnin@mail.ru
Belozersky Institute of Physico-Chemical Biology
Russian Federation, 119992 MoscowS. V. Boichuk
Kazan State Medical University; Russian Medical Academy of Continuous Professional Education
Email: pbkopnin@mail.ru
Department of Pathology, Department of Radiotherapy and Radiology
Russian Federation, 420012 Kazan; 119454 MoscowI. I. Eremin
Petrovsky National Research Center of Surgery
Email: pbkopnin@mail.ru
Russian Federation, 119991 Moscow
N. V. Khromova
N. N. Blokhin National Medical Research Center of Oncology
Email: pbkopnin@mail.ru
Scientific Research Institute of Carcinogenesis
Russian Federation, 115478 MoscowP. B. Kopnin
N. N. Blokhin National Medical Research Center of Oncology
Author for correspondence.
Email: pbkopnin@mail.ru
Scientific Research Institute of Carcinogenesis
Russian Federation, 115478 MoscowReferences
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