{rfName}
Tr

Indexed in

License and use

Icono OpenAccess

Altmetrics

Grant support

Research conducted for this publication was supported by the Ministerio de Econom'a y Competitividad (BFU2016-78951-R , BFU2017-90578-REDT) , Comunidad de Madrid (B2017/BMD-3684) , Ministerio de Ciencia , Innovacio'n y Universidades (MICINN RTI2018-095166-B-I00) , Karolinska Institutet and the Albert Renold Travel Fellowship Programme from the European Association for the Study of Diabetes.

Analysis of institutional authors

Lanzon, BAuthorGarcia-Carrasco, AAuthorIzquierdo-Lahuerta, AAuthorTorres, LAuthorCorrales, PAuthorRos, MAuthorMedina-Gomez, GCorresponding Author

Share

September 27, 2022
Publications
>
Article

Transforming growth factor beta 3 deficiency promotes defective lipid metabolism and fibrosis in murine kidney

Publicated to:Disease Models & Mechanisms. 14 (9): dmm048249- - 2021-09-01 14(9), DOI: 10.1242/dmm.048249

Authors: Escasany, Elia; Lanzon, Borja; Garcia-Carrasco, Almudena; Izquierdo-Lahuerta, Adriana; Torres, Lucia; Corrales, Patricia; Rodriguez, Ana Elena Rodriguez; Luis-Lima, Sergio; Alvarez, Concepcion Martinez; Ruperez, Francisco Javier; Ros, Manuel; Porrini, Esteban; Ryden, Mikael; Medina-Gomez, Gema

Affiliations

CEU Univ, Univ San Pablo CEU, Urbanizac Monteprincipe, Ctr Metab & Bioanal CEMBIO,Fac Farm, Madrid 28660, Spain - Author
Hosp Univ Islas Canarias, Unidad Invest, Tenerife 38320, Spain - Author
IIS Fdn Jimenez Diaz, Dept Nefrol & Hipertens, Madrid 28040, Spain - Author
Karolinska Univ Hosp, Karolinska Inst, Dept Med, S-14186 Stockholm, Sweden - Author
Univ Complutense Madrid, Fac Med, Dept Anat & Embriol, Madrid 28040, Spain - Author
Univ La Laguna, Inst Tecnol Biomed ITB, Tenerife 38200, Spain - Author
Univ Rey Juan Carlos, Dept Ciencias Basicas Salud, Fac Ciencias Salud, Area Bioquim & Biol Mol,LAFEMEX Lab, Avda Atenas S-N, Madrid 28922, Spain - Author
Univ Rey Juan Carlos, Fac Ciencias Salud, Dept Ciencias Basicas Salud, Lipobeta Grp,Area Bioquim & Biol Mol, Avda Atenas S-N, Madrid 28922, Spain - Author
See more

Abstract

Glomerulosclerosis and tubulointerstitial fibrosis are pathological features of chronic kidney disease. Transforming growth factor beta (TGF beta) is a key player in the development of fibrosis. However, of the three known TGF beta isoforms, only TGF beta 1 has an established role in fibrosis, and the pathophysiological relevance of TGF beta 2 and TGF beta 3 is unknown. Because Tgfb3 deficiency in mice results in early postnatal lethality, we analyzed the kidney phenotype of heterozygous Tgfb3-knockout mice (Tgfb3(+/-)) and compared it with that of matched wild-type mice. Four-month-old Tgfb3(+/-) mice exhibited incipient renal fibrosis with epithelial-mesenchymal transition, in addition to glomerular basement membrane thickening and podocyte foot process effacement associated with albuminuria. Also evident was insulin resistance and oxidative stress at the renal level, together with aberrant renal lipid metabolism and mitochondrial function. Omics analysis revealed toxic species, such as diacylglycerides and ceramides, and dysregulated mitochondrial metabolism in Tgfb3(+/-) mice. Kidneys of Tgfb3(+/-) mice showed morphological alterations of mitochondria and overactivation of non-canonical MAPK ERK1/2 and JNK cascades. Our study indicates that renal TGF beta 3 might have antifibrotic and renoprotective properties, opposing or counteracting the activity of TGF beta 1. This article has an associated First Person interview with the first author of the paper.

Keywords

AlbuminuriaAnimalAnimal cellAnimal experimentAnimal modelAnimalsAntifibrotic activityArticleCeramideCkdCollagen gene-transcriptionControlled studyDiabetic-nephropathyDiacylglycerolDown regulationEnzyme activityEpithelial mesenchymal transitionExpressionFactor-beta-3FibrosisGlomerulus basement membraneHumanHumansInjuryInsulin resistanceKidneyKidney fibrosisKnockout mouseLipid metabolismLipid storageMaleMetabolismMetabolomicsMiceMice, knockoutMitochondriaMitochondrial respirationMitogen activated protein kinase 3MouseNonhumanOmicsOxidative stressPhenotypePodocyteProtein deficiencyQuantificationRenal protectionSignal transductionStress activated protein kinaseTgfTgf betaTgf-betaTgfb3 protein, mouseTgfβTransforming growth factor betaTransforming growth factor beta1Transforming growth factor beta3

Quality index

Bibliometric impact. Analysis of the contribution and dissemination channel

The work has been published in the journal Disease Models & Mechanisms due to its progression and the good impact it has achieved in recent years, according to the agency WoS (JCR), it has become a reference in its field. In the year of publication of the work, 2021, it was in position 13/77, thus managing to position itself as a Q1 (Primer Cuartil), in the category Pathology.

From a relative perspective, and based on the normalized impact indicator calculated from World Citations provided by WoS (ESI, Clarivate), it yields a value for the citation normalization relative to the expected citation rate of: 1.33. This indicates that, compared to works in the same discipline and in the same year of publication, it ranks as a work cited above average. (source consulted: ESI Nov 14, 2024)

This information is reinforced by other indicators of the same type, which, although dynamic over time and dependent on the set of average global citations at the time of their calculation, consistently position the work at some point among the top 50% most cited in its field:

  • Field Citation Ratio (FCR) from Dimensions: 2.85 (source consulted: Dimensions Jul 2025)

Specifically, and according to different indexing agencies, this work has accumulated citations as of 2025-07-26, the following number of citations:

  • WoS: 13
  • Scopus: 15
  • Europe PMC: 7

Impact and social visibility

From the perspective of influence or social adoption, and based on metrics associated with mentions and interactions provided by agencies specializing in calculating the so-called "Alternative or Social Metrics," we can highlight as of 2025-07-26:

  • The use, from an academic perspective evidenced by the Altmetric agency indicator referring to aggregations made by the personal bibliographic manager Mendeley, gives us a total of: 20.
  • The use of this contribution in bookmarks, code forks, additions to favorite lists for recurrent reading, as well as general views, indicates that someone is using the publication as a basis for their current work. This may be a notable indicator of future more formal and academic citations. This claim is supported by the result of the "Capture" indicator, which yields a total of: 28 (PlumX).

With a more dissemination-oriented intent and targeting more general audiences, we can observe other more global scores such as:

  • The Total Score from Altmetric: 5.6.
  • The number of mentions on the social network X (formerly Twitter): 11 (Altmetric).

It is essential to present evidence supporting full alignment with institutional principles and guidelines on Open Science and the Conservation and Dissemination of Intellectual Heritage. A clear example of this is:

  • The work has been submitted to a journal whose editorial policy allows open Open Access publication.

Leadership analysis of institutional authors

This work has been carried out with international collaboration, specifically with researchers from: Sweden.

There is a significant leadership presence as some of the institution’s authors appear as the first or last signer, detailed as follows: First Author () and Last Author (Medina Gómez, Maria Gema).

the author responsible for correspondence tasks has been Medina Gómez, Maria Gema.