Matrix protein Tenascin-C promotes kidney fibrosis via STAT3 activation in response to tubular injury

Xie, Qionghong; Zhang, Min; Mao, Xiaoyi; Xu, Mingyue; Liu, Shaojun; Shang, Da; Xu, Yunyu; Chen, Ruiying; Guan, Yi; Huang, Xinzhong; Zent, Roy; Pozzi, Ambra; Hao, Chuan‐Ming

doi:10.1038/s41419-022-05496-z

Cited by 9 publications

(4 citation statements)

References 67 publications

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“…TNC is the rst member of the tenascin family to be discovered, which mainly mediates cell adhesion and extracellular matrix 17 . As reported, TNC can modulate cell cycle of neural stem cells 18 , promote brosis in tubular injury of kidney 19 , and take part in ovarian cancer migration 20 . But the role of TNC + broblasts in human skin diseases is completely unknown.…”

Section: Introductionmentioning

confidence: 76%

TNC+ fibroblasts involve in skin inflammation via neuro-immune and interacting with T cells

Hu,

Zhao,

Zhang

et al. 2023

Preprint

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Background Neuro-immune interactions play a crucial role in the pathogenesis of various skin diseases, TNC + fibroblasts are recently identified as key participants in this process in psoriasis. However, the molecular mechanisms underlying their impacts on different skin diseases remain poorly understood. Methods We collected Bulk RNA-Seq/Array data, single cell and spatial RNA-Seq data of more than 20 skin diseases from public databases and processed them using several bioinformatics tools, then identified the key functions, transcription factors, cell trajectory of TNC + fibroblasts, and the interactions between TNC + fibroblasts and immune cells, thus revealed the role and molecular mechanisms about TNC + fibroblasts involving in neuro-immune in skin diseases. Results Our analysis found that TNC + fibroblasts and neuro-immune involved in different skin diseases, especially inflammation and tumors. TNC was correlated to inflammatory genes and immune cell infiltration, its over-expression was a crucial feature of inflammatory fibroblasts in skin diseases. TNC + fibroblasts had intensive interactions with different immune cell, especially T cells, mainly through ligand-receptor pairs such as collegens-CD44. We further found that inflammatory and cellular structure-related functions were activated in TNC + fibroblasts, transcription factors EPAS1, HIF1A, and STAT1 could be main intermediates. Besides, the molecular patterns were varied in different diseases. Conclusions Our study sheds light on the molecular mechanisms underlying neuro-immune interactions in skin diseases and provides new insights into the role of TNC + fibroblasts in inducing skin abnormalities, especially inflammation.

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Section: Introductionmentioning

confidence: 76%

TNC+ fibroblasts involve in skin inflammation via neuro-immune and interacting with T cells

Hu,

Zhao,

Zhang

et al. 2023

Preprint

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“…At the same time, more and more studies have confirmed the functions of THBS2 in diverse fibrosis, even in PF [41][42][43][44]. FAP and TNC genes as biomarkers have been proved in liver fibrosis and kidney fibrosis [45,46]. The relative RNA expression and protein levels of ADAMTS16 elevated in mice with cardiac fibrosis [47].…”

Section: Discussionmentioning

confidence: 98%

The Identification Markers of activated myofibroblast subsets in the Human Lung Fibrosis Ecosystem via integrated omics Analysis

Zheng,

Song,

et al. 2024

Preprint

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Background: The aberrant remodeling of the extracellular matrix (ECM) is closely associated with lung fibrosis. However, the mechanisms underlying ECM remodeling in pulmonary fibrosis (PF) remain unclear. The advent of single-cell RNA sequencing (scRNA-seq) has provided valuable insights into the diverse phenotypic and functional characteristics of human PF. Nevertheless, the dynamic of ECM remodeling in terms of ECM synthesizing and the potential activating markers of myofibroblasts in the human PF microenvironment still needs to be investigated. Methods: We performed integrative scRNA-seq analyses on high-fidelity PF data from a public platform by filtering out the low-quality counts and doublets using two doublet prediction methods. Next, we investigated the dynamic of the ECM signature in diverse cells in PF and screened the potential markers of myofibroblasts via fitting a successful polynomial regression model. Finally, the markers of activated myofibroblasts were identified using bulk RNA-seq of pulmonary tissue. Results: First, we depicted the pathogenic landscape and demonstrated the heterogeneity of ECM in PF by integratively analyzing single-cell RNA-seq data, and we hypothesized that myofibroblasts played a significant role in ECM formation. Second, our results successfully displayed the biological dynamic changes of ECM and investigated the 73 positive correlated genes of myofibroblasts in PF via a polynomial regression model. Then, the bulk RNA-seq results further identified eight new activating markers of myofibroblasts, such as MFAP2, MXRA5, and LRRC17 via transcriptomic signature, correlation and ROC scores. Finally, the results of cell-cell interaction indicated that myeloid cells may be involved in regulating ECM remodeling through proliferation mediated by myofibroblasts that secrete POSTN, suggesting that ECM remodeling in PF is a complex and multi-participated process. Conclusions: In summary, we provided insights into the contributions of ECM in human PF by integrative analysis and highlighted potential clinical utilities of myofibroblast subsets as therapeutic targets.

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“…Ретинол-связывающий белок и кининоген-1 являются маркерами повреждения клеток тубулярного эпителия и, по данным других авторов, факторами, ассоциированными с отсутствием ответа на стероиды [21,22]. Об интенсивности накопления ЭЦМ свидетельствует выделение с мочой больных с ФСГС люмикана, тенасцина X и нейрофилина-2 [23][24][25].…”

Section: Discussionunclassified

Study of urinary markers of different podocytopathies by proteomic analysis

Vinogradov,

Chebotareva,

Bugrova

et al. 2023

Terapevticheskii arkhiv

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Background. Focal segmental glomerulosclerosis (FSGS) is a primary podocytopathy characterized by primary podocyte detection and high proteinuria. The search for biomarkers and factors associated with the progression of this disease is an important task nowdays. Aim. To assess the proteomic profile of urine in patients with FSGS and to isolate urinary biomarkers of podocytopathies. Materials and methods. The study included 41 patients diagnosed with chronic glomerulonephritis, 27 men and 14 women. According to the morphological study, 28 patients were diagnosed with FSGS, 9 with steroid-sensitive nephrotic syndrome and 14 with steroid-resistant nephrotic syndrome. The comparison group included 13 patients with membranous nephropathy. The study of the urinary proteome was carried out by targeted liquid chromatography-mass spectrometry using multiple reaction monitoring with synthetic stable isotope labelled peptide standards. Results. The main differences in the protein profile of urine were found in the subgroups of steroid-sensitive (SS) and steroid-resistant (SR) FSGS. In the FSGS SR group, at the onset of the disease, there was a high concentration of proteins reflecting damage to the glomerular filter (apo-lipoprotein A-IV, orosomucoid, cadherin, hemopexin, vitronectin), as well as proteins associated with tubulo-interstitial inflammation and accumulation of extracellular matrix (retinol- and vitamin D-binding proteins, kininogen-1, lumican and neurophilin-2). Compared with the membranous nephropathy group, FSGS patients had significantly higher urinary concentrations of carnosinase, orosomucoid, cadherin-13, tenascin X, osteopontin, and zinc-alpha-2-glycoprotein. Conclusion. Thus, in patients with SR FSGS, the proteomic profile of urine includes more proteins at elevated concentrations, which reflects severe damage to various parts of the nephron compared with patients with SS FSGS and membranous nephropathy.

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Matrix protein Tenascin-C promotes kidney fibrosis via STAT3 activation in response to tubular injury

Cited by 9 publications

References 67 publications

TNC+ fibroblasts involve in skin inflammation via neuro-immune and interacting with T cells

TNC+ fibroblasts involve in skin inflammation via neuro-immune and interacting with T cells

The Identification Markers of activated myofibroblast subsets in the Human Lung Fibrosis Ecosystem via integrated omics Analysis

Study of urinary markers of different podocytopathies by proteomic analysis

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