Myofibroblasts: Master of disguise

Bagalad, Bhavana S; Kumar, Kirthi; Puneeth, H K

doi:10.4103/jomfp.jomfp_146_15

Cited by 43 publications

(55 citation statements)

References 33 publications

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“…[11][12][13] Astonishingly, long-term use of classical antiglaucoma medication increases the risk of filtering failure caused by scar formation in patients who have undergone filtering surgery. 19,[26][27][28] In addition, mitogen-activated protein kinase (MAPK), associated with the development of renal fibrosis, 29 pulmonary fibrosis, 30 and latanoprost-induced human Tenon fibroblast (HTF) contractility, 14 is activated by TGF-β. [15][16][17] TGF-β causes activation and proliferation of resident fibroblasts, as well as their migration into damaged tissue 11,18,19 ; this causes a change to the myofibroblast phenotype.…”

Section: Introductionmentioning

confidence: 99%

An in vitro study of scarring formation mediated by human Tenon fibroblasts: Effect of Y‐27632, a Rho kinase inhibitor

Ibrahim

Iwata

et al. 2019

Cell Biochemistry & Function

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Scar formation is the most common cause for failure of glaucoma filtration surgery because of increased fibroblast proliferation and activation. We have now examined the effect of Y‐27632, a Rho‐associated protein kinase (ROCK) inhibitor, on postsurgical scarring formation in human Tenon fibroblasts (HTFs). Collagen gel contraction assay was used to compare contractility activity of Y‐27632 with several antiglaucoma drugs. Immunofluorescence and western blotting were used to examine expression of scar formation–related factors. We found that Y‐27632 inhibited collagen gel contraction, as well as α‐smooth muscle actin and vimentin expression; these were promoted by treatment with latanoprost, timolol, or transforming growth factor (TGF)–β. To investigate the effect of Y‐27632 in postsurgical scarring, we mimicked TGF‐β secretion by stimulating HTFs with TGF‐β prior to Y‐27632 treatment. HTFs cultured in the presence of TGF‐β significantly increased gel contraction. In contrast, when HTFs were treated with 10μM Y‐27632, contraction was significantly inhibited. Furthermore, Y‐27632 reduced TGF‐β–induced phosphorylation of mitogen‐activated protein kinase signalling. These results suggest that ROCK inhibitors may inhibit fibrosis by inhibiting transdifferentiation of Tenon fibroblasts into myofibroblasts and by inhibiting TGF‐β signalling after surgery through mitogen‐activated protein kinase pathway suppression. These results implicate that ROCK inhibitors may improve outcomes after filtering surgery with a potential antiscarring effect, while latanoprost and timolol may induce fibrosis. Significance of the study Scar formation is the primary cause of failure after glaucoma filtration surgery. A ROCK inhibitor, Y‐27632, has been introduced as a novel potential antiglaucoma treatment to reduce intraocular pressure. The aim of our study was to elucidate the effect of Y‐27632 on scarring formation after glaucoma filtration surgery, in direct comparison with other antiglaucoma drugs. Our findings thus suggested that Y‐27632 may inhibit fibrosis and improve outcome after glaucoma filtration surgery through inhibition of transdifferentiation of Tenon fibroblasts into myofibroblasts, and the TGF‐β and MAPK signalling after surgery, while latanoprost and timolol may induce fibrosis.

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Section: Introductionmentioning

confidence: 99%

An in vitro study of scarring formation mediated by human Tenon fibroblasts: Effect of Y‐27632, a Rho kinase inhibitor

Ibrahim

Iwata

et al. 2019

Cell Biochemistry & Function

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“…This phenomenon is comparable to skin wounds, where only few myofibroblasts are present in early granulation tissue, but are numerous in later stages . The multiplication of myofibroblasts and the subsequent immoderate matrix synthesis has been attributed to the killing of Fas+ lymphocytes, which confers myofibroblasts an immune‐privileged cell phenotype as they escape immune surveillance and evade apoptosis in the chronic scarring process . In the present study, the presence of myofibroblasts in OSMF was evaluated through α‐SMA immunoexpression in varying grades of OSMF.…”

Section: Discussionmentioning

confidence: 81%

“…Less generally appreciated is the notion that the transformation of fibroblasts to myofibroblasts is a key, perhaps essential, event for this uncontained collagen production and deposition . Myofibroblasts are modified fibroblasts armed with myosin and SMA and exert contractile forces to condense the size of the wound . They can originate from various cells, such as local fibroblasts, pericytes, smooth muscle cells, epithelial cells, endothelial cells, hepatic perisinusoidal cells, mesenchymal stem cells, and fibrocytes.…”

Section: Discussionmentioning

confidence: 99%

“…This fibronectin ED‐A domain is necessary for TGF‐β1 to trigger α‐SMA expression and secretion of collagen by myofibroblasts. Following the activation of myofibroblast, tumor necrosis factor‐α, interleukin (IL)‐1, IL‐6, IL‐8, Transforming growth factor‐beta (TGF‐ß), Epidermal growth factor (EGF), Fibroblast growth factor (FGF), Insulin‐like growth factor I and II (IGF‐I and II) promote myofibroblast proliferation . Therefore, in the present study we also attempted to assess the correlation of serum TGF‐β1 levels with clinicopathological parameters of the study cases.…”

Section: Discussionmentioning

confidence: 99%

“…1 Myofibroblasts are modified fibroblasts armed with myosin and SMA and exert contractile forces to condense the size of the wound. 9 They can originate from various cells, such as local fibroblasts, pericytes, smooth muscle cells, epithelial cells, endothelial cells, hepatic perisinusoidal cells, mesenchymal stem cells, and fibrocytes. Myofibroblasts are essential for the veracity of the mammalian body because of their role in inflammation and repair, but can also become a threat by their ability to increase tumor development.…”

Section: Discussionmentioning

confidence: 99%

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Immunoexpression of alpha smooth muscle actin correlates with serum transforming growth factor‐β1 levels in oral submucous fibrosis

Singh¹,

Juneja²,

Tandon³

et al. 2019

J of Invest & Clin Dent

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Aim The aim of the present study was to correlate the immunoexpression of alpha‐smooth muscle actin (α‐SMA) for myofibroblasts with the serum levels of transforming growth factor‐β1 (TGF‐β1) in oral submucous fibrosis (OSMF). Methods A total of 100 cases of histopathologically confirmed OSMF were assessed for α‐SMA expression. Clinical data, such as age, sex, mouth opening, and habit history, were obtained for each case. Serum TGF‐β1 levels were recorded in 73 patients with the help of enzymelinked immunosorbent assay technique. Results The staining index of α‐SMA increased concomitantly with higher myofibroblast count in the increasing histopathological grades of OSMF (P ≤ .05). Serum TGF‐β1 levels were highest in the intermediate grades of OSMF. Clinical parameters, such as mouth opening, cheek flexibility, and tongue protrusion, showed a direct correlation with increasing clinical grades of OSMF. Conclusions The progressive increase in myofibroblasts from early to advanced stages suggests their potential use as markers for evaluating the severity of OSMF. Additionally, as myofibroblasts are responsible for producing a variety of factors that are involved in the fibrotic processes; they could be the key link in the pathogenesis of OSMF. Interruption of their development, recruitment, or activation could provide a unique therapeutic target for future treatment options in patients with OSMF.

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Fibrotic remodeling and tissue regeneration mechanisms define the therapeutic potential of human muscular progenitors

Hsiao

Wang

Yang

2022

Bioengineering & Transla Med

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Fibrosis is an intrinsic biological reaction toward the challenges of tissue injury that is implicated in the wound‐healing process. Although it is useful to efficiently mitigate the damage, progression of fibrosis is responsible for the morbidity and mortality occurring in a variety of diseases. Because of lacking effective treatments, there is an emerging need for exploring antifibrotic strategies. Cell therapy based on stem/progenitor cells is regarded as a promising approach for treating fibrotic diseases. Appropriate selection of cellular sources is required for beneficial results. Muscle precursor cells (MPCs) are specialized progenitors harvested from skeletal muscle for conducting muscle regeneration. Whether they are also effective in regulating fibrosis has seldom been explored and merits further investigation. MPCs were successfully harvested from all human samples regardless of demographic backgrounds. The extracellular matrices remodeling was enhanced through the paracrine effects mediated by MPCs. The suppression effects on fibrosis were confirmed in vivo when MPCs were transplanted into the diseased animals with oral submucous fibrosis. The data shown here revealed the potential of MPCs to be employed to simultaneously regulate both processes of fibrosis and tissue regeneration, supporting them as the promising cell candidates for development of the cell therapy for antifibrosis and tissue regeneration.

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Myofibroblasts: Master of disguise

Cited by 43 publications

References 33 publications

An in vitro study of scarring formation mediated by human Tenon fibroblasts: Effect of Y‐27632, a Rho kinase inhibitor

An in vitro study of scarring formation mediated by human Tenon fibroblasts: Effect of Y‐27632, a Rho kinase inhibitor

Immunoexpression of alpha smooth muscle actin correlates with serum transforming growth factor‐β1 levels in oral submucous fibrosis

Fibrotic remodeling and tissue regeneration mechanisms define the therapeutic potential of human muscular progenitors

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