Organ Fibrosis and Autoimmunity: The Role of Inflammation in TGFβ-Dependent EMT

Sisto, Margherita; Ribatti, Doménico; Lisi, Sabrina

doi:10.3390/biom11020310

Cited by 83 publications

(76 citation statements)

References 237 publications

(184 reference statements)

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“…Alterations in the cellular junction integrity lead to significant changes in salivary gland epithelial cells polarity and organization that may affect secretory functionality [ 19 ]. This scenario fits well with the inflammatory-related EMT activation program observed in SS, characterized by a loss of epithelial markers, such as E-cadherin and tight junction proteins [ 20 , 21 , 22 ]. All these phenomena, potentially implicated in the reduction of the normal quality and quantity of saliva in SS, resulted in accelerated development of SG inflammation [ 18 , 19 ].…”

Section: Sjögren’s Syndrome Featuressupporting

confidence: 81%

Sjögren’s Syndrome-Related Organs Fibrosis: Hypotheses and Realities

Sisto

Ribatti

Lisi

2022

JCM

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Sjögren’s syndrome (SS) is a systemic chronic autoimmune disorder characterized by lymphoplasmacytic infiltration of salivary glands (SGs) and lacrimal glands, causing glandular damage. The disease shows a combination of dryness symptoms found in the oral cavity, pharynx, larynx, and vagina, representing a systemic disease. Recent advances link chronic inflammation with SG fibrosis, based on a molecular mechanism pointing to the epithelial to mesenchymal transition (EMT). The continued activation of inflammatory-dependent fibrosis is highly detrimental and a common final pathway of numerous disease states. The important question of whether and how fibrosis contributes to SS pathogenesis is currently intensely debated. Here, we collect the recent findings on EMT-dependent fibrosis in SS SGs and explore clinical evidence of multi-organ fibrosis in SS to highlight potential avenues for therapeutic investigation.

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Section: Sjögren’s Syndrome Featuressupporting

confidence: 81%

Sjögren’s Syndrome-Related Organs Fibrosis: Hypotheses and Realities

Sisto

Ribatti

Lisi

2022

JCM

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“…Interestingly, EMT (type II) was also found to be induced in response to inflammation, for example during wound healing, tissue regeneration, and fibrosis [ 1 , 4 , 6 , 12 ]. EMT-like event has been found to occur during wound healing, where keratinocytes at the border of the wound undergo partial EMT and acquire a metastable state.…”

Section: Introductionmentioning

confidence: 99%

Epithelial–mesenchymal transition and its transcription factors

et al. 2021

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Epithelial-mesenchymal transition or EMT is an extremely dynamic process involved in conversion of epithelial cells into mesenchymal cells, stimulated by an ensemble of signaling pathways, leading to change in cellular morphology, suppression of epithelial characters and acquisition of properties such as enhanced cell motility and invasiveness, reduced cell death by apoptosis, resistance to chemotherapeutic drugs etc. Significantly, EMT has been found to play a crucial role during embryonic development, tissue fibrosis and would healing, as well as during cancer metastasis. Over the years, work from various laboratories have identified a rather large number of transcription factors including the master regulators of EMT, with the ability to regulate the EMT process directly. In this review, we put together these EMT transcription factors and discussed their role in the process. We have also tried to focus on their mechanism of action, their inter-dependency, and the large regulatory network they form. Subsequently, it has become clear that the composition and structure of the transcriptional regulatory network behind EMT probably varies based upon various physiological and pathological contexts, or even in a cell/tissue type dependent manner.

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“…EMT is involved in a variety of biological processes, such as tissue repair and pathology, including cancer and cataract (Sisto et al, 2021). It also plays an important role in the progression of fibrotic diseases.…”

Section: Discussionmentioning

confidence: 99%

Ketamine Induced Bladder Fibrosis Through MTDH/P38 MAPK/EMT Pathway

Zhu

et al. 2022

Front. Pharmacol.

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Purpose: Ketamine is an anesthetic in clinical, but it has also been used as an abusing drug due to its low price and hallucinogenic effects. It is proved that ketamine abusing would cause multiple system damage including the urinary system, which is called ketamine-induced cystitis (KIC). Bladder fibrosis is late stage in KIC and threaten abusers’ life. This study aimed to investigate the molecular mechanism of ketamine-induced bladder fibrosis.Methods: Female Sprague Dawley (SD) rats were randomly divided into 3 groups. 2 groups were treated with tail vein injection of ketamine (25 mg/kg/day, 50 mg/kg/day ketamine hydrochloride solution, respectively) for 12 weeks, whereas the control group was treated with normal saline solution. In each group, rat bladders were extracted and samples were examined for pathological and morphological alterations via hematoxylin and eosin (HE) staining, Masson’s trichrome staining and immunohistochemistry (IHC). SV-HUC-1 cells were treated with different concentrations of ketamine solution (0, 0.1, 0.5, 1 mmol/L). Rat bladder and SV-HUC-1 cells were extracted protein and RNA for Western blot and RT-PCR detection. Metadherin (MTDH) siRNAs and overexpression plasmids were used to knock down and overexpress the relative genes. P38 mitogen-activated protein kinase (MAPK) inhibitor was utilized to inhibit the MAPK pathway.Results: Rats in the ketamine group exhibited fibrosis compared to rats of the control group and fibrosis were also markedly upregulated in SV-HUC-1 cells after treated with ketamine, which were ketamine concentration-dependent. After treating with ketamine in SV-HUC-1 cells, there was an increase expression of MTDH, epithelial-mesenchymal transition (EMT) markers, P38 MAPK. MTDH knockdown would suppresses P38 MAPK/EMT pathway to inhibit fibrosis, however, MTDH overexpression could promote the pathway in SV-HUC-1 cells.Conclusion: In rats and SV-HUC-1 cells ketamine-treated models, MTDH can regulate EMT through the P38 MAPK pathway to regulate the process of bladder fibrosis.

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Organ Fibrosis and Autoimmunity: The Role of Inflammation in TGFβ-Dependent EMT

Cited by 83 publications

References 237 publications

Sjögren’s Syndrome-Related Organs Fibrosis: Hypotheses and Realities

Sjögren’s Syndrome-Related Organs Fibrosis: Hypotheses and Realities

Epithelial–mesenchymal transition and its transcription factors

Ketamine Induced Bladder Fibrosis Through MTDH/P38 MAPK/EMT Pathway

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