Pub Date : 2022-05-13DOI: 10.1007/s00018-022-04317-y
Tom Van Loy, Steven De Jonghe, Karolien Castermans, Wouter Dheedene, Reinout Stoop, Lars Verschuren, Matthias Versele, Patrick Chaltin, Aernout Luttun, Dominique Schols
Atypical chemokine receptor 3 (ACKR3, formerly CXC chemokine receptor 7) is a G protein-coupled receptor that recruits β-arrestins, but is devoid of functional G protein signaling after receptor stimulation. In preclinical models of liver and lung fibrosis, ACKR3 was previously shown to be upregulated after acute injury in liver sinusoidal and pulmonary capillary endothelial cells, respectively. This upregulation was linked with a pro-regenerative and anti-fibrotic role for ACKR3. A recently described ACKR3-targeting small molecule agonist protected mice from isoproterenol-induced cardiac fibrosis. Here, we aimed to evaluate its protective role in preclinical models of liver and lung fibrosis. After confirming its in vitro pharmacological activity (i.e., ACKR3-mediated β-arrestin recruitment and receptor binding), in vivo administration of this ACKR3 agonist led to increased mouse CXCL12 plasma levels, indicating in vivo interaction of the agonist with ACKR3. Whereas twice daily in vivo administration of the ACKR3 agonist lacked inhibitory effect on bleomycin-induced lung fibrosis, it had a modest, but significant anti-fibrotic effect in the carbon tetrachloride (CCl4)-induced liver fibrosis model. In the latter model, ACKR3 stimulation affected the expression of several fibrosis-related genes and led to reduced collagen content as determined by picro-sirius red staining and hydroxyproline quantification. These data confirm that ACKR3 agonism, at least to some extent, attenuates fibrosis, although this effect is rather modest and heterogeneous across various tissue types. Stimulating ACKR3 alone without intervening in other signaling pathways involved in the multicellular crosstalk leading to fibrosis will, therefore, most likely not be sufficient to deliver a satisfactory clinical outcome.
{"title":"Stimulation of the atypical chemokine receptor 3 (ACKR3) by a small-molecule agonist attenuates fibrosis in a preclinical liver but not lung injury model.","authors":"Tom Van Loy, Steven De Jonghe, Karolien Castermans, Wouter Dheedene, Reinout Stoop, Lars Verschuren, Matthias Versele, Patrick Chaltin, Aernout Luttun, Dominique Schols","doi":"10.1007/s00018-022-04317-y","DOIUrl":"10.1007/s00018-022-04317-y","url":null,"abstract":"<p><p>Atypical chemokine receptor 3 (ACKR3, formerly CXC chemokine receptor 7) is a G protein-coupled receptor that recruits β-arrestins, but is devoid of functional G protein signaling after receptor stimulation. In preclinical models of liver and lung fibrosis, ACKR3 was previously shown to be upregulated after acute injury in liver sinusoidal and pulmonary capillary endothelial cells, respectively. This upregulation was linked with a pro-regenerative and anti-fibrotic role for ACKR3. A recently described ACKR3-targeting small molecule agonist protected mice from isoproterenol-induced cardiac fibrosis. Here, we aimed to evaluate its protective role in preclinical models of liver and lung fibrosis. After confirming its in vitro pharmacological activity (i.e., ACKR3-mediated β-arrestin recruitment and receptor binding), in vivo administration of this ACKR3 agonist led to increased mouse CXCL12 plasma levels, indicating in vivo interaction of the agonist with ACKR3. Whereas twice daily in vivo administration of the ACKR3 agonist lacked inhibitory effect on bleomycin-induced lung fibrosis, it had a modest, but significant anti-fibrotic effect in the carbon tetrachloride (CCl<sub>4</sub>)-induced liver fibrosis model. In the latter model, ACKR3 stimulation affected the expression of several fibrosis-related genes and led to reduced collagen content as determined by picro-sirius red staining and hydroxyproline quantification. These data confirm that ACKR3 agonism, at least to some extent, attenuates fibrosis, although this effect is rather modest and heterogeneous across various tissue types. Stimulating ACKR3 alone without intervening in other signaling pathways involved in the multicellular crosstalk leading to fibrosis will, therefore, most likely not be sufficient to deliver a satisfactory clinical outcome.</p>","PeriodicalId":15854,"journal":{"name":"Journal of Geometry","volume":"108 1","pages":"293"},"PeriodicalIF":8.0,"publicationDate":"2022-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9106635/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73702227","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-04-29DOI: 10.1007/s00022-022-00639-1
Jian Liu
{"title":"Correction to: On the fundamental triangle inequality and Gerretsen’s double inequality","authors":"Jian Liu","doi":"10.1007/s00022-022-00639-1","DOIUrl":"https://doi.org/10.1007/s00022-022-00639-1","url":null,"abstract":"","PeriodicalId":15854,"journal":{"name":"Journal of Geometry","volume":" ","pages":""},"PeriodicalIF":0.6,"publicationDate":"2022-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47266319","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-04-25DOI: 10.1007/s00022-022-00660-4
Leah Wrenn Berman, G'abor G'evay, Tomavz Pisanski
{"title":"New bounds on the existence of $$(n_{5})$$ and $$(n_{6})$$ configurations: the Grünbaum Calculus revisited","authors":"Leah Wrenn Berman, G'abor G'evay, Tomavz Pisanski","doi":"10.1007/s00022-022-00660-4","DOIUrl":"https://doi.org/10.1007/s00022-022-00660-4","url":null,"abstract":"","PeriodicalId":15854,"journal":{"name":"Journal of Geometry","volume":"77 1","pages":""},"PeriodicalIF":0.6,"publicationDate":"2022-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41276345","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-04-20DOI: 10.1007/s00022-023-00672-8
F. Ihringer
{"title":"Non-geometric cospectral mates of line graphs with a linear representation","authors":"F. Ihringer","doi":"10.1007/s00022-023-00672-8","DOIUrl":"https://doi.org/10.1007/s00022-023-00672-8","url":null,"abstract":"","PeriodicalId":15854,"journal":{"name":"Journal of Geometry","volume":"114 1","pages":"1-5"},"PeriodicalIF":0.6,"publicationDate":"2022-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45304943","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-04-13DOI: 10.1007/s00022-023-00673-7
S. Honda, Masatomo Takahashi, Haiou Yu
{"title":"Bertrand and Mannheim curves of framed curves in the 4-dimensional Euclidean space","authors":"S. Honda, Masatomo Takahashi, Haiou Yu","doi":"10.1007/s00022-023-00673-7","DOIUrl":"https://doi.org/10.1007/s00022-023-00673-7","url":null,"abstract":"","PeriodicalId":15854,"journal":{"name":"Journal of Geometry","volume":"114 1","pages":"1-24"},"PeriodicalIF":0.6,"publicationDate":"2022-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48343058","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-04-03DOI: 10.1007/s00022-022-00654-2
Csaba Vincze, M. Ol'ah
{"title":"Finsler metrics and semi-symmetric compatible linear connections","authors":"Csaba Vincze, M. Ol'ah","doi":"10.1007/s00022-022-00654-2","DOIUrl":"https://doi.org/10.1007/s00022-022-00654-2","url":null,"abstract":"","PeriodicalId":15854,"journal":{"name":"Journal of Geometry","volume":" ","pages":""},"PeriodicalIF":0.6,"publicationDate":"2022-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45051048","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-04-02DOI: 10.1007/s00022-022-00638-2
P. Sousa, B. P. Lima, B. M. Vieira
{"title":"Generalized translation hypersurfaces in conformally flat spaces","authors":"P. Sousa, B. P. Lima, B. M. Vieira","doi":"10.1007/s00022-022-00638-2","DOIUrl":"https://doi.org/10.1007/s00022-022-00638-2","url":null,"abstract":"","PeriodicalId":15854,"journal":{"name":"Journal of Geometry","volume":" ","pages":""},"PeriodicalIF":0.6,"publicationDate":"2022-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45847262","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-03-13DOI: 10.1007/s00022-022-00634-6
S. Alesker
{"title":"On convergence of intrinsic volumes of Riemannian manifolds","authors":"S. Alesker","doi":"10.1007/s00022-022-00634-6","DOIUrl":"https://doi.org/10.1007/s00022-022-00634-6","url":null,"abstract":"","PeriodicalId":15854,"journal":{"name":"Journal of Geometry","volume":"113 1","pages":""},"PeriodicalIF":0.6,"publicationDate":"2022-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"52082918","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-03-04DOI: 10.1007/s00022-022-00631-9
Huili Liu, Yixuan Liu, S. Jung
{"title":"Ruled invariants and total classification of non-developable ruled surfaces","authors":"Huili Liu, Yixuan Liu, S. Jung","doi":"10.1007/s00022-022-00631-9","DOIUrl":"https://doi.org/10.1007/s00022-022-00631-9","url":null,"abstract":"","PeriodicalId":15854,"journal":{"name":"Journal of Geometry","volume":"113 1","pages":""},"PeriodicalIF":0.6,"publicationDate":"2022-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"52082802","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-02-26DOI: 10.1007/s00022-022-00635-5
H. F. Lima, F. R. Santos, L. S. Rocha
{"title":"Sharp Simons type integral inequalities for closed linear Weingarten submanifolds in a space form","authors":"H. F. Lima, F. R. Santos, L. S. Rocha","doi":"10.1007/s00022-022-00635-5","DOIUrl":"https://doi.org/10.1007/s00022-022-00635-5","url":null,"abstract":"","PeriodicalId":15854,"journal":{"name":"Journal of Geometry","volume":"113 1","pages":""},"PeriodicalIF":0.6,"publicationDate":"2022-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"52083028","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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