Cathelicidin Treatment Silences Epithelial–Mesenchymal Transition Involved in Pulmonary Fibrosis in a Murine Model of Hypersensitivity Pneumonitis

Lemieszek, Marta Kinga; Golec, Marcin; Zwoliński, Jacek; Dutkiewicz, Jacek; Milanowski, Janusz

doi:10.3390/ijms232113039

Cited by 3 publications

(3 citation statements)

References 60 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Snail1/RhoA/α-SMA pathway is a proven mechanism involved in fibroblast activation [ 12 ], and several studies have demonstrated that Snail1 participated in organ fibrosis, i.e., renal fibrosis, cardiac fibrosis, and lung fibrosis [ 10 , 22 , 23 ]. On the basis of these observations, the role of Snail1 in FBXL8-regulated myofibroblast differentiation is to be investigated.…”

Section: Resultsmentioning

confidence: 99%

“…Snail1 is a zinc finger transcription factor, which is not normally expressed in adult fibroblasts, but highly expressed in myofibroblasts [ 11 ]. Substantial evidence has proved that Snail1 plays a crucial role in EMT and is associated with organ fibrosis, such as lung and renal fibrosis [ 22 , 23 ]. Recently, Stanisavljevic et al provided additional insight into the role of Snail1 in CFs activation, and Snail1-deleted fibroblast failed to gain myofibroblast characteristics, such as α-SMA expression and collagen secretion [ 12 ].…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

FBXL8 inhibits post-myocardial infarction cardiac fibrosis by targeting Snail1 for ubiquitin-proteasome degradation

Li,

Zuo,

et al. 2024

Cell Death Dis

View full text Add to dashboard Cite

Abnormal cardiac fibrosis is the main pathological change of post-myocardial infarction (MI) heart failure. Although the E3 ubiquitin ligase FBXL8 is a key regulator in the cell cycle, cell proliferation, and inflammation, its role in post-MI ventricular fibrosis and heart failure remains unknown. FBXL8 was primarily expressed in cardiac fibroblasts (CFs) and remarkably decreased in CFs treated by TGFβ and heart subjected to MI. The echocardiography and histology data suggested that adeno-associated viruses (AAV9)-mediated FBXL8 overexpression had improved cardiac function and ameliorated post-MI cardiac fibrosis. In vitro, FBXL8 overexpression prevented TGFβ-induced proliferation, migration, contraction, and collagen secretion in CFs, while knockdown of FBXL8 demonstrated opposite effects. Mechanistically, FBXL8 interacted with Snail1 to promote Snail1 degradation through the ubiquitin–proteasome system and decreased the activation of RhoA. Moreover, the FBXL8ΔC3 binding domain was indispensable for Snail1 interaction and degradation. Ectopic Snail1 expression partly abolished the effects mediated by FBXL8 overexpression in CFs treated by TGFβ. These results characterized the role of FBXL8 in regulating the ubiquitin-mediated degradation of Snail1 and revealed the underlying molecular mechanism of how MI up-regulated the myofibroblasts differentiation-inducer Snail1 and suggested that FBXL8 may be a potential curative target for improving post-MI cardiac function.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

FBXL8 inhibits post-myocardial infarction cardiac fibrosis by targeting Snail1 for ubiquitin-proteasome degradation

Li,

Zuo,

et al. 2024

Cell Death Dis

View full text Add to dashboard Cite

show abstract

“…Injured epithelial cells or cells can acquire migration capacity similar to that of mesenchymal cells through epithelial‐mesenchymal transition (EMT)/endothelial‐mesenchymal transition (EndoMT), and subsequently differentiate into MFBs. In addition, circulating fibroblast‐like cells and mesenchymal stem cells (MSCs) both show the capacity to transdifferentiate into MFBs [23].…”

Section: Introduction To Pathological Mechanisms Of Rifmentioning

confidence: 99%

Radiation‐induced fibrosis: Mechanisms and therapeutic strategies from an immune microenvironment perspective

Zheng,

Liu,

2024

Immunology

View full text Add to dashboard Cite

Radiation‐induced fibrosis (RIF) is a severe chronic complication of radiotherapy (RT) manifested by excessive extracellular matrix (ECM) components deposition within the irradiated area. The lung, heart, skin, jaw, pelvic organs and so on may be affected by RIF, which hampers body functions and quality of life. There is accumulating evidence suggesting that the immune microenvironment may play a key regulatory role in RIF. This article discussed the synergetic or antagonistic effects of immune cells and mediators in regulating RIF's development. Several potential preventative and therapeutic strategies for RIF were proposed based on the immunological mechanisms to provide clinicians with improved cognition and clinical treatment guidance.

show abstract

Beneficial Impact of Inhaled 25(OH)-Vitamin D3 and 1,25(OH)2-Vitamin D3 on Pulmonary Response in the Murine Model of Hypersensitivity Pneumonitis

Lemieszek,

Chojnacki,

Paśnik

et al. 2024

IJMS

View full text Add to dashboard Cite

Despite numerous scientific reports on the negative impact of vitamin D3 deficiency on many respiratory diseases, little is known about the influence of this phenomenon on the development and progression of hypersensitivity pneumonitis (HP). The presented study is an attempt to shed light on this occurrence. The research was performed on mouse strain C57BL/6J exposed to the antigen of Pantoea agglomerans (etiological factor of HP). To induce vitamin D3 deficiency, mice received a diet with a 10 times lower amount of cholecalciferol than the main control group. VD3-deficient mice inhaled 25(OH)-VD3 or 1,25(OH)2-VD3 used separately or with SE-PA. At the beginning of the experiment and after 14 and 28 days of inhalation, respiratory function was examined using whole-body plethysmography. Moreover, at indicated time points, mice were sacrificed and samples collected for histological examination, flow cytometry, and ELISA. The performed study revealed that inhalations with 25(OH)-VD3 and 1,25(OH)2-VD3 effectively eliminated most of the negative changes in the respiratory system caused by vitamin D3 deficiency by restoring the physiological concentration of 1,25(OH)2-VD3 in the body. VD3-deficient mice which inhaled P. agglomerans antigen and vitamin D3 metabolites also demonstrated the ability of the tested compounds to eliminate, or at least weaken, the negative effects of the HP causative factor and desired effect, including improvement of respiratory functions and attenuation of inflammation and signs of fibrosis. The obtained results suggested that the beneficial influence of inhaled vitamin D3 metabolites on HP development was associated with the restoration of the physiological concentration of 1,25(OH)2-VD3 in the pulmonary compartments in VD3-deficient mice.

show abstract

Cathelicidin Treatment Silences Epithelial–Mesenchymal Transition Involved in Pulmonary Fibrosis in a Murine Model of Hypersensitivity Pneumonitis

Cited by 3 publications

References 60 publications

FBXL8 inhibits post-myocardial infarction cardiac fibrosis by targeting Snail1 for ubiquitin-proteasome degradation

FBXL8 inhibits post-myocardial infarction cardiac fibrosis by targeting Snail1 for ubiquitin-proteasome degradation

Radiation‐induced fibrosis: Mechanisms and therapeutic strategies from an immune microenvironment perspective

Beneficial Impact of Inhaled 25(OH)-Vitamin D3 and 1,25(OH)2-Vitamin D3 on Pulmonary Response in the Murine Model of Hypersensitivity Pneumonitis

Contact Info

Product

Resources

About