Molecular imaging of fibrosis: recent advances and future directions

Montesi, Sydney B.; Désogère, Pauline; Fuchs, Bryan C.; Caravan, Peter

doi:10.1172/jci122132

Cited by 95 publications

(85 citation statements)

References 104 publications

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“…Collagen can also be used for the imaging of targeted sites. Imaging of the collagen content and arrangement is conducive to the assessment of tissue stiffness, metabolism, and drug resistance [196][197][198], and technology to utilize these data is currently under development [199]; for instance, magnetic resonance apparent diffusion coefficient values were used to indicate a negative correlation of collagen with esophageal SCC cells [200]. The label-free Raman spectroscopic measurements used to distinguish radiation-sensitive tumors were based on differences in collagen content [201].…”

Section: Subtype Of Mmps Associated Collagen Pathological Functions Omentioning

confidence: 99%

The role of collagen in cancer: from bench to bedside

et al. 2019

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Collagen is the major component of the tumor microenvironment and participates in cancer fibrosis. Collagen biosynthesis can be regulated by cancer cells through mutated genes, transcription factors, signaling pathways and receptors; furthermore, collagen can influence tumor cell behavior through integrins, discoidin domain receptors, tyrosine kinase receptors, and some signaling pathways. Exosomes and microRNAs are closely associated with collagen in cancer. Hypoxia, which is common in collagen-rich conditions, intensifies cancer progression, and other substances in the extracellular matrix, such as fibronectin, hyaluronic acid, laminin, and matrix metalloproteinases, interact with collagen to influence cancer cell activity. Macrophages, lymphocytes, and fibroblasts play a role with collagen in cancer immunity and progression. Microscopic changes in collagen content within cancer cells and matrix cells and in other molecules ultimately contribute to the mutual feedback loop that influences prognosis, recurrence, and resistance in cancer. Nanoparticles, nanoplatforms, and nanoenzymes exhibit the expected gratifying properties. The pathophysiological functions of collagen in diverse cancers illustrate the dual roles of collagen and provide promising therapeutic options that can be readily translated from bench to bedside. The emerging understanding of the structural properties and functions of collagen in cancer will guide the development of new strategies for anticancer therapy.

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Section: Subtype Of Mmps Associated Collagen Pathological Functions Omentioning

confidence: 99%

The role of collagen in cancer: from bench to bedside

et al. 2019

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“…However targeting TGF-β is problematic due to its diverse roles in cell proliferation and differentiation, wound healing and in the immune system [33]. Although several targeting strategies have been proven effective in renal fibrosis animal models, there are no novel therapeutic targets that have demonstrated safety and efficacy in preventing or alleviating renal fibrosis in humans [34]. One important reason is that rodent models often do not fully mimic the human clinical situation and only a few studies have used more than one model to verify their findings [35].…”

Section: Discussionmentioning

confidence: 99%

NMDA Receptor-mediated CaMKII/ERK Activation Contributes to Renal Fibrosis

Zhou

Liu

Guo

et al. 2020

Preprint

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Background: Renal fibrosis (RF) results in renal function impairment and eventually kidney failure. We found that N-methyl-D-aspartate receptor (NMDAR) played an important role during RF. However, its mechanism of action is yet to be deciphered. Methods: Acute RF was induced in mice by unilateral ureteral obstruction (UUO). NR1, which is the functional subunit of NMDAR, was downregulated using lentiviral vector-mediated shRNA interference. Histological changes were observed by Masson’s trichrome staining. Expression of NR1, fibrotic and EMT markers were measured by immunohistochemistry and western blot analysis. HK-2 cells were incubated with TGF-β, and NMDAR antagonist MK-801 and Ca2+/calmodulin-dependent protein kinase II (CaMKII) antagonist KN-93 administration were further included in this study for pathway determination. Expression of NR1, total and phosphorylated CaMKII, total and phosphorylated ERK were measured using western blot and immunofluorescent assays. Chronic renal fibrosis was introduced by sublethal ischemia-reperfusion injury in mice, and oral NMDAR inhibitor dextromethorphan (DXM) administration was performed. Results: NR1 expressions were upregulated in both obstructed kidneys and TGF-β treated HK-2 cells. NR1 knockdown, DXM, MK801, and KN93 reduced the fibrotic morphology in vivo and in vitro respectively, and companied with the downregulated ERK activation, while KN93 administration had no effect on NR1 and CaMKII levels. Conclusions: NMDAR participates in both acute and chronic renal fibrogenesis via CaMKII/ERK activation, and is a potential therapeutic target for renal fibrosis.

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“…However targeting TGF-β is problematic due to its diverse roles in cell proliferation and differentiation, wound healing and in the immune system [33]. Although several targeting strategies have been proven effective in renal brosis animal models, there are no novel therapeutic targets that have demonstrated safety and e cacy in preventing or alleviating renal brosis in humans [34]. One important reason is that rodent models often do not fully mimic the human clinical situation and only a few studies have used more than one model to verify their ndings [35].…”

Section: Discussionmentioning

confidence: 99%

NMDA Receptor-mediated CaMKII/ERK Activation Contributes to Renal Fibrosis

Zhou

Liu

Guo

et al. 2020

Preprint

View full text Add to dashboard Cite

Background: Renal fibrosis (RF) results in renal function impairment and eventually kidney failure. We found that N-methyl-D-aspartate receptor (NMDAR) played an important role during RF. However, its mechanism of action is yet to be deciphered. Methods: Acute RF was induced in mice by unilateral ureteral obstruction (UUO). NR1, which is the functional subunit of NMDAR, was downregulated using lentiviral vector-mediated shRNA interference. Histological changes were observed by Masson’s trichrome staining. Expression of NR1, fibrotic and EMT markers were measured by immunohistochemistry and western blot analysis. HK-2 cells were incubated with TGF-β, and NMDAR antagonist MK-801 and Ca2+/calmodulin-dependent protein kinase II (CaMKII) antagonist KN-93 administration were further included in this study for pathway determination. Expression of NR1, total and phosphorylated CaMKII, total and phosphorylated ERK were measured using western blot and immunofluorescent assays. Chronic renal fibrosis was introduced by sublethal ischemia-reperfusion injury in mice, and oral NMDAR inhibitor dextromethorphan (DXM) administration was performed. Results: NR1 expressions were upregulated in both obstructed kidneys and TGF-β treated HK-2 cells. NR1 knockdown, MK801 and KN93 reduced the fibrotic morphology in vivo and in vitro respectively, and companied with the downregulated ERK activation, while KN93 administration had no effect on NR1 and CaMKII levels. Mice in the DXM group had better preservation of kidney structures and corticomedullary volumes. Conclusions: NMDAR participates in both acute and chronic renal fibrogenesis via CaMKII/ERK activation, and is a potential therapeutic target for renal fibrosis.

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Molecular imaging of fibrosis: recent advances and future directions

Cited by 95 publications

References 104 publications

The role of collagen in cancer: from bench to bedside

The role of collagen in cancer: from bench to bedside

NMDA Receptor-mediated CaMKII/ERK Activation Contributes to Renal Fibrosis

NMDA Receptor-mediated CaMKII/ERK Activation Contributes to Renal Fibrosis

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