The bright side of fibroblasts: molecular signature and regenerative cues in major organs

Gomes, Rita N.; Manuel, Filipa; Nascimento, Diana S.

doi:10.1038/s41536-021-00153-z

Cited by 87 publications

(62 citation statements)

References 235 publications

(249 reference statements)

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“…Tissue fibrosis is a pathologic process, in general, injury tissues are able to restore normal organ architecture and function ( 11 ). However, if there is a dysregulation between the inflammation, the proliferative or the remodeling stages under physiological conditions, the tissue injury signals will be triggered so that contribute to fibrosis, even resulting in organ dysfunction ( 12 ).…”

Section: Regulation Of Grk2 Activity Under Pathophysiology Conditionsmentioning

confidence: 99%

G Protein-Coupled Receptor Kinase 2 as Novel Therapeutic Target in Fibrotic Diseases

Shan

et al. 2022

Front. Immunol.

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G protein-coupled receptor kinase 2 (GRK2), an important subtype of GRKs, specifically phosphorylates agonist-activated G protein-coupled receptors (GPCRs). Besides, current research confirms that it participates in multiple regulation of diverse cells via a non-phosphorylated pathway, including interacting with various non-receptor substrates and binding partners. Fibrosis is a common pathophysiological phenomenon in the repair process of many tissues due to various pathogenic factors such as inflammation, injury, drugs, etc. The characteristics of fibrosis are the activation of fibroblasts leading to myofibroblast proliferation and differentiation, subsequent aggerate excessive deposition of extracellular matrix (ECM). Then, a positive feedback loop is occurred between tissue stiffness caused by ECM and fibroblasts, ultimately resulting in distortion of organ architecture and function. At present, GRK2, which has been described as a multifunctional protein, regulates copious signaling pathways under pathophysiological conditions correlated with fibrotic diseases. Along with GRK2-mediated regulation, there are diverse effects on the growth and apoptosis of different cells, inflammatory response and deposition of ECM, which are essential in organ fibrosis progression. This review is to highlight the relationship between GRK2 and fibrotic diseases based on recent research. It is becoming more convincing that GRK2 could be considered as a potential therapeutic target in many fibrotic diseases.

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Section: Regulation Of Grk2 Activity Under Pathophysiology Conditionsmentioning

confidence: 99%

G Protein-Coupled Receptor Kinase 2 as Novel Therapeutic Target in Fibrotic Diseases

Shan

et al. 2022

Front. Immunol.

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“…The lack of transformation in the transfected HDFs could result by the function of hTERT in circumventing telomere-controlled senescence and SV40 in cell-cycle regulation without inducing global chromosomal instability. Key dermal fibroblast markers, including COL1A1, COL3A1, Elastin and Vimentin, were constantly expressed in the immortalized HDFs, indicating the maintenance of the typical fibroblast property, and the potential application in studying skin biology (35). On the other hand, SIRT1 and p53 were highly expressed in transfected HDFs, which suggests their involvement in cell immortalization.…”

Section: Discussionmentioning

confidence: 94%

Transgenic Immortalization of Human Dermal Fibroblasts Mediated Through the MicroRNA/SIRT1 Pathway

Promjantuek

Chaicharoenaudomrung

Phonchai

et al. 2021

In Vivo

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Background/Aim: Human dermal fibroblasts (HDFs) are widely used as a skin model in cosmetic and pharmaceutical industry due their advantages for the cosmetic industry and medical aspects. Telomeres are key players in controlling cellular aging, in which telomeres and the telomerase enzyme (hTERT) can maintain proliferative capacity and prolong cellular senescence. The primary aim of the study was to elucidate the underlying mechanisms of hTERT/SV40 immortalization of human dermal fibroblasts. Materials and Methods: Transgenic expression of hTERT and SV40 large antigen, as well as co-transfection of both factors was performed and their significance evaluated in terms of HDF immortalization efficiency. Results: The results showed that the immortalized fibroblasts of all conditions can be cultured in over 60 passages and maintain their telomere length. Further, key markers of skin cells, such as COL1A1, KRT18 and ELASTIN, were up-regulated in immortalized cells. In addition, p53 expression was enhanced in all immortalized cells, in accordance with activation of the SIRT1 gene upon transgenic immortalization. The significant role of SIRT1 in fibroblast proliferation was assessed by shRNA-knockdown, and it was found that SIRT1 silencing led to loss of Ki67, a proliferation marker. Moreover, miR-93, a SIRT1-targeted miRNA, also had a significantly reduced expression in the co-transfected immortalized cells, highlighting the linkage of the miRNA and SIRT1 pathway in the immortalization of human dermal fibroblasts. Conclusion: This evidence from this study could benefit the efficient development of human skin cell lines for use in the cosmetic industry in the future.The expansion of somatic cells in vitro for research and medical applications is limited by their short proliferative lifespan (1). Cellular senescence is a state of irreversible arrest of cell proliferation, exhibiting enlarged morphological changes and senescence-associated heterochromatin foci formation. Senescence, originating from the Latin word 'SENAX', refers to a physiological program towards permanent cell-cycle arrest. Cellular senescence can be stimulated via a variety of factors, such as tumour suppressor proteins, oncogene activation, telomere shortening, genomic DNA damage, and activation of the p53/p21 pathway. Oncogene-induced senescence is a cellular response found in pre-malignant tumours. Senescent cells exert a pleotropic effect on development, tissue aging and regeneration, inflammation, wound healing and tumour suppression (2). Currently, cosmeceutical research is developed to correct skin problems, including skin aging, skin inflammation, skin disorders, and acne. In cosmetics, human skin cells are used as a standard model for demonstrating the therapeutic potential of cosmetic products. The use of in vitro tests is a critical step in the development of new products for treating skin problems. The study of human skin cell biology has increased the hope for a successful cell therapy in aesthetic medicine and cosmetics. Various types of ...

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“…Oral barrier tissue is composed of oral epithelial cells [67], distinct gingival and periodontal ligament fibroblasts [68], and oral immune cells [55]. In addition, osteoblastic progenitor cells are primarily localized in the periodontal ligament space [69].…”

Section: Cellular Source Of Rankl In the Oral Barrier Tissuementioning

confidence: 99%

Current perspectives of residual ridge resorption: Pathological activation of oral barrier osteoclasts

et al. 2023

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Tooth extraction is a last resort treatment for resolving pathological complications of dentition induced by infection and injury. Although the extraction wound generally heals uneventfully, resulting in the formation of an edentulous residual ridge, some patients experience long-term and severe residual ridge reduction. The objective of this review was to provide a contemporary understanding of the molecular and cellular mechanisms that may potentially cause edentulous jawbone resorption. Study selection: Clinical, in vivo, and in vitro studies related to the characterization of and cellular and molecular mechanisms leading to residual ridge resorption. Results:The alveolar processes of the maxillary and mandibular bones uniquely juxtapose the gingival tissue. The gingival oral mucosa is an active barrier tissue that maintains homeostasis of the internal organs through its unique barrier immunity. Tooth extraction not only generates a bony socket but also injures oral barrier tissue. In response to wounding, the alveolar bone socket initiates regeneration and remodeling through coupled bone formation and osteoclastic resorption. Osteoclasts are also found on the external surface of the alveolar bone, interfacing the oral barrier tissue. Osteoclasts in the oral barrier region are not coupled with osteoblastic bone formation and often remain active long after the completion of wound healing, leading to a net decrease in the alveolar bone structure. Conclusion:The novel concept of oral barrier osteoclasts may provide important clues for future clinical strategies to maintain residual ridges for successful prosthodontic and restorative therapies.

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The bright side of fibroblasts: molecular signature and regenerative cues in major organs

Cited by 87 publications

References 235 publications

G Protein-Coupled Receptor Kinase 2 as Novel Therapeutic Target in Fibrotic Diseases

G Protein-Coupled Receptor Kinase 2 as Novel Therapeutic Target in Fibrotic Diseases

Transgenic Immortalization of Human Dermal Fibroblasts Mediated Through the MicroRNA/SIRT1 Pathway

Current perspectives of residual ridge resorption: Pathological activation of oral barrier osteoclasts

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