Journal of Cell Communication and Signaling最新文献

{"title":"Cooperation is the key: the CCN biological system as a gate to high complex protein superfamilies’ signaling","authors":"Bernard Perbal,&nbsp;Matthieu Perbal,&nbsp;Annick Perbal","doi":"10.1007/s12079-023-00749-8","DOIUrl":"10.1007/s12079-023-00749-8","url":null,"abstract":"<div>\u0000 \u0000 <p>Cellular signaling is generally understood as the support of communication between contiguous cells belonging to the same tissue or cells being far apart of each other, at a molecular scale, when the message emitted by the transmitters is traveling in liquid or solid matter to reach recipient targets. Subcellular signaling is also important to ensure the proper cell constitution and functioning. However cell signaling is mostly used in the first understanding, to describe how the message sent from one point to another one, will reach a target where it will be interpreted. The Cellular Communication Network (CCN) factors (Perbal et al. 2018) constitute a family of biological regulators thought to be responsible for signaling pathways coordination (Perbal 2018). Indeed, these proteins interact with a diverse group of cell receptors, such as integrins, low density lipoprotein receptors, heparan sulfate proteoglycan receptors (HSPG), and the immunoglobulin superfamily expressed exclusively in the nervous system, or with soluble factors such as bone morphogenetic proteins (BMPS) and other growth factors such as vascular endothelial growth factor, fibroblastic growth factor, and transforming growth factor (TGFbeta). Starting from the recapitulation of basic concepts in enzymology and protein-ligands interactions, we consider, in this manuscript, interpretations of the mechanistic interactions that have been put forward to explain the diversity of CCN proteins biological activities. We suggest that the cross-talks between superfamilies of proteins under the control of CCNs might play a central role in the coordination of developmental signaling pathways\u0000</p>\u0000 </div>","PeriodicalId":15226,"journal":{"name":"Journal of Cell Communication and Signaling","volume":"17 2","pages":"233-253"},"PeriodicalIF":4.1,"publicationDate":"2023-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10326204/pdf/12079_2023_Article_749.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9795719","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Quinacrine inhibits cMET-mediated metastasis and angiogenesis in breast cancer stem cells","authors":"Biswajit Das,&nbsp;Chinmayee Sethy,&nbsp;Subhajit Chatterjee,&nbsp;Somya Ranjan Dash,&nbsp;Saptarshi Sinha,&nbsp;Subarno Paul,&nbsp;Kunal Goutam,&nbsp;Chanakya Nath Kundu","doi":"10.1007/s12079-023-00756-9","DOIUrl":"10.1007/s12079-023-00756-9","url":null,"abstract":"<div>\u0000 \u0000 <p>A trans-membrane receptor tyrosine kinase, cMET, belonging to the MET proto-oncogene family, is responsible for cancer metastasis and angiogenesis. But not much is known about the role of cMET in growth and progression of cancer stem cells (CSCs). Earlier studies have shown that Quinacrine (QC), a bioactive agent, has anti-CSCs activity. Here, the role of QC in deregulation of cMET-mediated metastasis and angiogenesis has been systematically evaluated in vitro in highly metastatic breast CSCs (mBCSCs), ex vivo in patient-derived breast cancer stem cells (PDBCSCs) and in vivo in xenograft mice model systems. Cell proliferation, migration, invasion and representative metastasis markers were upregulated in cMET-overexpressed cells and QC exposure inhibited these processes in both mBCSCs and PDBCSCs. Interestingly, metastasis was significantly inhibited by QC in cMET-overexpressed cells but comparatively lesser significant alteration of the process was noted in cMET-silenced cells. Increase in vascularization (in in ovo CAM assay), and cell–cell tube formation (in HUVECs), and enhanced MMP9 and MMP2 enzymatic activities (in gelatin zymography) were noted after cMET overexpression but these processes got reversed after cMET knockdown or QC treatment in cMET-overexpressed cells. QC inhibited angiogenesis significantly in cMET-overexpressed cells, but lesser significant change was observed in cMET-silenced cells. Reduction in tumor volume and decreased expression of metastatic and angiogenic markers were also noted in xenograft mice after QC treatment. Furthermore, QC inhibited cMET activity by dephosphorylation of its tyrosine residues (Y1234 and Y1356) and downregulation of its downstream cascade. Thus, QC inhibited the cMET-mediated metastasis and angiogenesis in in vitro, in ovo, in vivo and ex vivo model systems.\u0000</p>\u0000 </div>","PeriodicalId":15226,"journal":{"name":"Journal of Cell Communication and Signaling","volume":"17 4","pages":"1371-1388"},"PeriodicalIF":3.6,"publicationDate":"2023-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10713934/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9809006","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction to: Three generations of mTOR kinase inhibitors in the activation of the apoptosis process in melanoma cells","authors":"Dorota Ciołczyk-Wierzbicka,&nbsp;Agnieszka Krawczyk,&nbsp;Marta Zarzycka,&nbsp;Grzegorz Zemanek,&nbsp;Karol Wierzbicki","doi":"10.1007/s12079-023-00764-9","DOIUrl":"10.1007/s12079-023-00764-9","url":null,"abstract":"<p><b>Correction to: Journal of Cell Communication and Signaling</b></p><p>https://doi.org/10.1007/s12079-023-00748-9</p><p>In this article the author name Dorota Ciołczyk-Wierzbicka was incorrectly written as Dorota Ciołczyk-Wierzbica.</p><p>The original article has been corrected.</p>","PeriodicalId":15226,"journal":{"name":"Journal of Cell Communication and Signaling","volume":"17 3","pages":"991"},"PeriodicalIF":4.1,"publicationDate":"2023-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10409933/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9960517","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Temperal and spatial expression of CCN1, CCN3, CCN4, CCN5 and CCN6 proteins in the developing postnatal teeth","authors":"Shubo Li,&nbsp;Shufang Li","doi":"10.1007/s12079-023-00758-7","DOIUrl":"10.1007/s12079-023-00758-7","url":null,"abstract":"<div>\u0000 \u0000 <p>CCN proteins are matricellular proteins and are important modulators of development and function of adult organs. However, there is no literature reporting the localization of CCN proteins during postnatal tooth development and the formation of periodontium. Therefore, the aim of our study was to investigate the expression of CCN1, CCN3, CCN4, CCN5 and CCN6 in the developing postnatal teeth. Wistar rats were used at postnatal (PN) 3.5, 7, 16 and 21 days and maxillas were processed for immunohistochemistry. At PN3.5 and PN7, preameloblasts (PA), secretory ameloblasts (SA), odontoblasts (OD) and dental pulp (DP) showed moderate to strong staining for CCN1, CCN4 and CCN6 respectively. CCN5 was intensely expressed in predentin, whereas CCN5 was undetectable in PA, SA, OD and DP. At PN16 and PN21, moderate to strong reaction with CCN1, CCN4 and CCN6 was evident in OD, DP, reduced enamel epithelium (REE), osteoblasts (OB) and periodontal ligament (PDL) respectively, while CCN5 was negative to weakly expressed in REE, OD, DP, OB, PDL and osteocytes (OC). Interestingly, the expression of CCN1, CCN4 and CCN6 was initially negative at PN16 but strong at PN21 in OC. Furthermore, there was no staining for CCN3 in the tissues studied. These results demonstrated that the expression pattern of CCN1, CCN4 and CCN6 is similar and inversely correlated with that of CCN3. CCN5 exhibits a unique distribution pattern. These data indicate that CCN proteins might play regulatory roles in amelogenesis, dentinogenesis, osteogenesis and PDL homeostasis.</p>\u0000 </div>","PeriodicalId":15226,"journal":{"name":"Journal of Cell Communication and Signaling","volume":"17 2","pages":"275-285"},"PeriodicalIF":4.1,"publicationDate":"2023-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10326235/pdf/12079_2023_Article_758.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9792927","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A network map of macrophage-stimulating protein (MSP) signaling","authors":"Diya Sanjeev,&nbsp;Shobha Dagamajalu,&nbsp;Vineetha Shaji,&nbsp;Mejo George,&nbsp;Yashwanth Subbannayya,&nbsp;T. S. Keshava Prasad,&nbsp;Rajesh Raju,&nbsp;Rex Devasahayam Arokia Balaya","doi":"10.1007/s12079-023-00755-w","DOIUrl":"10.1007/s12079-023-00755-w","url":null,"abstract":"<div>\u0000 \u0000 <p>Macrophage-stimulating protein (MSP), a serum-derived growth factor belonging to the plasminogen-related kringle domain family, is mainly produced by the liver and released into the blood. MSP is the only known ligand for RON (“Recepteur d'Origine Nantais”, also known as MST1R), which is a member of the receptor tyrosine kinase (RTK) family. MSP is associated with many pathological conditions, including cancer, inflammation, and fibrosis. Activation of the MSP/RON system regulates main downstream signaling pathways, including phosphatidylinositol 3-kinase/ AKT serine/threonine kinase/ (PI3-K/AKT), mitogen-activated protein kinases (MAPK), c-Jun N-terminal kinase (JNK) &amp; Focal adhesion kinase (FAK). These pathways are mainly involved in cell proliferation, survival, migration, invasion, angiogenesis &amp; chemoresistance. In this work, we created a pathway resource of signaling events mediated by MSP/RON considering its contribution to diseases. We provide an integrated pathway reaction map of MSP/RON that is composed of 113 proteins and 26 reactions based on the curation of data from the published literature. The consolidated pathway map of MSP/RON mediated signaling events contains seven molecular associations, 44 enzyme catalysis, 24 activation/inhibition, six translocation events, 38 gene regulation events, and forty-two protein expression events. The MSP/RON signaling pathway map can be freely accessible through the WikiPathways Database URL: https://classic.wikipathways.org/index.php/Pathway:WP5353.</p>\u0000 </div>","PeriodicalId":15226,"journal":{"name":"Journal of Cell Communication and Signaling","volume":"17 3","pages":"1113-1120"},"PeriodicalIF":4.1,"publicationDate":"2023-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10409925/pdf/12079_2023_Article_755.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10507804","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"GSKIP modulates cell aggregation through EMT/MET signaling rather than differentiation in SH-SY5Y human neuroblastoma cells","authors":"Cheng-Yu Tsai,&nbsp;Huey-Jiun Ko,&nbsp;Shean-Jaw Chiou,&nbsp;Xin-Yi Lin,&nbsp;Tsung-Hsien Chuang,&nbsp;Jiin-Tsuey Cheng,&nbsp;Yu-Feng Su,&nbsp;Joon-Khim Loh,&nbsp;Yi-Ren Hong","doi":"10.1007/s12079-023-00752-z","DOIUrl":"10.1007/s12079-023-00752-z","url":null,"abstract":"<div>\u0000 \u0000 <p>GSK3β interacting protein (GSKIP) is a small A-kinase anchor protein previously reported to mediate the N-cadherin/β-catenin pool for differentiation in SH-SY5Y cells through overexpression of GSKIP to present the neuron outgrowth phenotype. To further investigate how GSKIP functions in neurons, CRISPR/Cas9 technology was utilized to knock out GSKIP (GSKIP-KO) in SH-SY5Y. Several GSKIP-KO clones resulted in an aggregation phenotype and reduced cell growth without retinoic acid (RA) treatment. However, neuron outgrowth was still observed in GSKIP-KO clones treated with RA. The GSKIP-KO clones exhibited an aggregation phenotype through suppression of GSK3β/β-catenin pathways and cell cycle progression rather than cell differentiation. Gene set enrichment analysis indicated that GSKIP-KO was related to epithelial mesenchymal transition/mesenchymal epithelial transition (EMT/MET) and Wnt/β-catenin/cadherin signaling pathways, suppressing cell migration and tumorigenesis through the inhibition of Wnt/β-catenin mediated EMT/MET. Conversely, reintroduction of GSKIP into GSKIP-KO clones restored cell migration and tumorigenesis. Notably, phosphor-β-catenin (S675) and β-catenin (S552) but not phosphor-β-catenin (S33/S37/T41) translocated into the nucleus for further gene activation. Collectively, these results suggested that GSKIP may function as an oncogene to form an aggregation phenotype for cell survival in harsh environments through EMT/MET rather than differentiation in the GSKIP-KO of SH-SY5Y cells.</p>\u0000 </div>","PeriodicalId":15226,"journal":{"name":"Journal of Cell Communication and Signaling","volume":"17 3","pages":"1039-1054"},"PeriodicalIF":4.1,"publicationDate":"2023-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10409706/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9967061","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CD40 induces selective routing of Ras isoforms to subcellular compartments","authors":"Arathi Nair,&nbsp;Sushmita Chakraborty,&nbsp;Bhaskar Saha","doi":"10.1007/s12079-023-00747-w","DOIUrl":"10.1007/s12079-023-00747-w","url":null,"abstract":"<div>\u0000 \u0000 <p>Ras GTPases are central to cellular signaling and oncogenesis. The three loci of the Ras gene encode for four protein isoforms namely Harvey-Ras (H-Ras), Kirsten-Ras (K-Ras 4A and 4B), and Neuroblastoma-Ras (N-Ras) which share ~ 80% sequence similarity and used to be considered functionally redundant. The small molecule inhibitors of Ras lack specificity for the isoforms leading to widespread toxicity in Ras-targeted therapeutics. Ras isoforms’ tissue-specific expression and selective association with carcinogenesis, embryonic development, and infection suggested their non-redundancy. We show that CD40, an antigen-presenting cell (APC)-expressed immune receptor, induces selective relocation of H-Ras, K-Ras, and N-Ras to the Plasma membrane (PM) lipid rafts, mitochondria, endoplasmic reticulum (ER), but not to the Golgi complex (GC). The two palmitoylated Ras isoforms—H-Ras and N-Ras—have a similar pattern of colocalization into the lipid-rich raft microdomain of the PM at early time points when compared to non-palmitoylated K-Ras (4B) with polylysine residues. CD40-induced trafficking of H-Ras and K-Ras to mitochondria and ER was found to be similar but different from that of N-Ras. Trafficking of all the Ras isoforms to the GC was independent of CD40 stimulation. The receptor-driven trafficking and spatial segregation of H-Ras, K-Ras, and N-Ras imply isoform-specific subcellular signaling platforms for the functional non-redundancy of Ras isoforms.</p>\u0000 </div>","PeriodicalId":15226,"journal":{"name":"Journal of Cell Communication and Signaling","volume":"17 3","pages":"1009-1021"},"PeriodicalIF":4.1,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10409697/pdf/12079_2023_Article_747.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10125452","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ephrin–Eph receptor tyrosine kinases for potential therapeutics against hepatic pathologies","authors":"Sowmya Mekala,&nbsp;Prachi Dugam,&nbsp;Amitava Das","doi":"10.1007/s12079-023-00750-1","DOIUrl":"10.1007/s12079-023-00750-1","url":null,"abstract":"<div>\u0000 \u0000 <p>Hepatic fibrosis is the common pathological change that occurs due to increased synthesis and accumulation of extracellular matrix components. Chronic insult from hepatotoxicants leads to liver cirrhosis, which if not reversed timely using appropriate therapeutics, liver transplantation remains the only effective therapy. Often the disease further progresses into hepatic carcinoma. Although there is an increased advancement in understanding the pathological phenotypes of the disease, additional knowledge of the novel molecular signaling mechanisms involved in the disease progression would enable the development of efficacious therapeutics. Ephrin–Eph molecules belong to the largest family of receptor tyrosine kinases (RTKs) which are identified to play a crucial role in cellular migratory functions, during morphological and developmental stages. Additionally, they contribute to the growth of a multicellular organism as well as in pathological conditions like cancer, and diabetes. A wide spectrum of mechanistic studies has been performed on ephrin–Eph RTKs in various hepatic tissues under both normal and diseased conditions revealing their diverse roles in hepatic pathology. This systematic review summarizes the liver-specific ephrin–Eph RTK signaling mechanisms and recognizes them as druggable targets for mitigating hepatic pathology.</p>\u0000 </div>","PeriodicalId":15226,"journal":{"name":"Journal of Cell Communication and Signaling","volume":"17 3","pages":"549-561"},"PeriodicalIF":4.1,"publicationDate":"2023-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10409970/pdf/12079_2023_Article_750.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10137446","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Three generations of mTOR kinase inhibitors in the activation of the apoptosis process in melanoma cells","authors":"Dorota Ciołczyk-Wierzbicka,&nbsp;Agnieszka Krawczyk,&nbsp;Marta Zarzycka,&nbsp;Grzegorz Zemanek,&nbsp;Karol Wierzbicki","doi":"10.1007/s12079-023-00748-9","DOIUrl":"10.1007/s12079-023-00748-9","url":null,"abstract":"<div>\u0000 \u0000 <p>Many signaling pathways are involved in the mammalian target of rapamycin (mTOR), and this serine/threonine kinase regulates the most important cellular processes such as cell proliferation, autophagy, and apoptosis. The subject of this research was the effect of protein kinase inhibitors involved in the AKT, MEK, and mTOR kinase signaling pathways on the expression of pro-survival proteins, activity of caspase-3, proliferation, and induction of apoptosis in melanoma cells. The following inhibitors were used: protein kinase inhibitors such as AKT—MK-2206, MEK—AS-703026, mTOR—everolimus and Torkinib, as well as dual PI3K and mTOR inhibitor—BEZ-235 and Omipalisib, and mTOR1/2—OSI-027 inhibitor in single-mode and their combinations with MEK1/2 kinase inhibitor AS-703026. The obtained results confirm the synergistic effect of nanomolar concentrations of mTOR inhibitors, especially the dual PI3K and mTOR inhibitors (Omipalisib, BEZ-235) in combination with the MAP kinase inhibitor (AS-703026) in the activation of caspase 3, induction of apoptosis, and inhibition of proliferation in melanoma cell lines. Our previous and current studies confirm the importance of the mTOR signal transduction pathway in the neoplastic transformation process. Melanoma is a case of a very heterogeneous neoplasm, which causes great difficulties in treating this neoplasm in an advanced stage, and the standard approach to this topic does not bring the expected results. There is a need for research on the search for new therapeutic strategies aimed at particular groups of patients.\u0000</p>\u0000 </div>","PeriodicalId":15226,"journal":{"name":"Journal of Cell Communication and Signaling","volume":"17 3","pages":"975-989"},"PeriodicalIF":4.1,"publicationDate":"2023-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10409930/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9972433","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Skin aging from the perspective of dermal fibroblasts: the interplay between the adaptation to the extracellular matrix microenvironment and cell autonomous processes","authors":"Gary J. Fisher,&nbsp;Bo Wang,&nbsp;Yilei Cui,&nbsp;Mai Shi,&nbsp;Yi Zhao,&nbsp;Taihao Quan,&nbsp;John J. Voorhees","doi":"10.1007/s12079-023-00743-0","DOIUrl":"10.1007/s12079-023-00743-0","url":null,"abstract":"<div>\u0000 \u0000 <p>This article summarizes important molecular mechanisms that drive aging in human skin from the perspective of dermal fibroblasts. The dermis comprises the bulk of the skin and is largely composed of a collagen-rich extracellular matrix (ECM). The dermal ECM provides mechanical strength, resiliency, and an environment that supports the functions of ibroblasts and other types of dermal cells. Fibroblasts produce the dermal ECM and maintain its homeostasis. Fibroblasts attach to the ECM and this attachment controls their morphology and function. During aging, the ECM undergoes gradual degradation that is nitiated by matrix metalloproteinases (MMPs). This degradation alters mechanical forces within the dermal ECM and disrupts he interactions between fibroblasts and the ECM thereby generating an aged fibroblast phenotype. This aged fibroblast phenotype is characterized by collapsed morphology, altered mechanosignaling, induction of CCN1, and activation of transcription factor AP-1, with consequent upregulation of target genes including MMPs and pro-inflammatory mediators. The TGF-beta pathway coordinately regulates ECM production and turnover. Altered mechanical forces, due to ECM fragmentation, down-regulate the type II TGF-beta receptor, thereby reducing ECM production and further increasing ECM breakdown. Thus, dermal aging involves a feed-forward process that reinforces the aged dermal fibroblast phenotype and promotes age-related dermal ECM deterioration. As discussed in the article, the expression of the aged dermal fibroblast phenotype involves both adaptive and cell-autonomous mechanisms.</p>\u0000 </div>","PeriodicalId":15226,"journal":{"name":"Journal of Cell Communication and Signaling","volume":"17 3","pages":"523-529"},"PeriodicalIF":4.1,"publicationDate":"2023-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10409944/pdf/12079_2023_Article_743.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10134020","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}