MicroRNAs in Mechanical Homeostasis

Herrera, Jeremy; Schwartz, Martin A.

doi:10.1101/cshperspect.a041220

Cited by 6 publications

(4 citation statements)

References 94 publications

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“…Of interest, mRNA for GOT2 , NDUFS3 , PGM1 , UQCRB , ALDH7A1 , HADH , and PSMD13 were significantly increased, but these were decreased at the protein expression level. These results likely reflect effects on translational efficiency of protein turnover ( 85 , 86 ). The authors concluded that FF are remarkably similar, independent of origin (UIP/IPF or sarcoidosis), consistent with this being a site of collagen biosynthesis.…”

Section: Discussionmentioning

confidence: 99%

The UIP/IPF fibroblastic focus is a collagen biosynthesis factory embedded in a distinct extracellular matrix

Herrera¹,

Dingle²,

Fernandez³

et al. 2022

JCI Insight

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Usual Interstitial Pneumonia (UIP) is a histological pattern characteristic of Idiopathic Pulmonary Fibrosis (IPF). The UIP pattern is patchy with histologically normal lung adjacent to dense fibrotic tissue. At this interface, fibroblastic foci (FF) are present and are sites where myofibroblasts and extracellular matrix (ECM) accumulate. Utilizing laser capture microdissection coupled mass spectrometry (LCM-MS), we interrogated the FF, adjacent mature scar, and adjacent alveoli in 6 fibrotic (UIP/IPF) specimens plus 6 nonfibrotic alveolar specimens as controls. The data were subject to qualitative and quantitative analysis, and histologically validated. We found that the fibrotic alveoli protein signature is defined by immune deregulation as the strongest category. The fibrotic mature scar classified as end-stage fibrosis whereas the FF contained an overabundance of a distinctive ECM compared to non-fibrotic control. Furthermore, the FF is positive for both TGFB1 and TGFB3, whereas the aberrant basaloid cell lining of the FF is predominantly positive for TGFB2. In conclusion, spatial proteomics demonstrated distinct protein compositions in the histologically defined regions of UIP/IPF tissue. These data revealed that the FF is the main site of collagen biosynthesis and that the adjacent alveoli are abnormal. This new and essential information will inform future mechanistic studies on fibrosis progression.

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Section: Discussionmentioning

confidence: 99%

The UIP/IPF fibroblastic focus is a collagen biosynthesis factory embedded in a distinct extracellular matrix

Herrera¹,

Dingle²,

Fernandez³

et al. 2022

JCI Insight

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“…In recent years, the predicted logarithmic relationship between vessel diameter and wall shear stress has been experimentally observed in the developing vasculature of zebrafish [15], though a similar relationship between pressure, metabolic signals, and vessel diameter has yet to be reported. Moreover, the assumption of a constant reference wall shear stress (τ ref ) throughout the cardiovascular system was recently put into question by the set-point theory of the Schwarz lab [84][85][86][87]. The expression for the wall shear stress dependence shown in Eq (1) has been maintained in subsequent iterations and implementation of logarithmic models; however, both the pressure and metabolic dependence have been updated in the years following this original publication [62,76].…”

Section: Modelling Paradigm 1: Logarithmic Models Of Vascular Calibre...mentioning

confidence: 99%

Mathematical models of developmental vascular remodelling: A review

Crawshaw¹,

Flegg²,

Bernabéu³

et al. 2023

PLoS Comput Biol

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Over the past 40 years, there has been a strong focus on the development of mathematical models of angiogenesis, while developmental remodelling has received little such attention from the mathematical community. Sprouting angiogenesis can be seen as a very crude way of laying out a primitive vessel network (the raw material), while remodelling (understood as pruning of redundant vessels, diameter control, and the establishment of vessel identity and hierarchy) is the key to turning that primitive network into a functional network. This multiscale problem is of prime importance in the development of a functional vasculature. In addition, defective remodelling (either during developmental remodelling or due to a reactivation of the remodelling programme caused by an injury) is associated with a significant number of diseases. In this review, we discuss existing mathematical models of developmental remodelling and explore the important contributions that these models have made to the field of vascular development. These mathematical models are effectively used to investigate and predict vascular development and are able to reproduce experimentally observable results. Moreover, these models provide a useful means of hypothesis generation and can explain the underlying mechanisms driving the observed structural and functional network development. However, developmental vascular remodelling is still a relatively new area in mathematical biology, and many biological questions remain unanswered. In this review, we present the existing modelling paradigms and define the key challenges for the field.

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“…Similarly, changes in shear stresses experienced by the endothelium have been shown to drive epigenetic effectors such as DNA methylation, histone modification, and expression of lncRNAs. Comprehensive discussion of these systems of mechanotransduction may be found elsewhere ( Ku et al, 2019 ; Herrera and Schwartz, 2022 ).…”

Section: Humoral and Biomechanical Drivers Of Endothelial Dysfunctionmentioning

confidence: 99%

Endothelial cell dysfunction in cardiac disease: driver or consequence?

Allbritton-King,

García-Cardeña

2023

Front. Cell Dev. Biol.

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The vascular endothelium is a multifunctional cellular system which directly influences blood components and cells within the vessel wall in a given tissue. Importantly, this cellular interface undergoes critical phenotypic changes in response to various biochemical and hemodynamic stimuli, driving several developmental and pathophysiological processes. Multiple studies have indicated a central role of the endothelium in the initiation, progression, and clinical outcomes of cardiac disease. In this review we synthesize the current understanding of endothelial function and dysfunction as mediators of the cardiomyocyte phenotype in the setting of distinct cardiac pathologies; outline existing in vivo and in vitro models where key features of endothelial cell dysfunction can be recapitulated; and discuss future directions for development of endothelium-targeted therapeutics for cardiac diseases with limited existing treatment options.

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MicroRNAs in Mechanical Homeostasis

Cited by 6 publications

References 94 publications

The UIP/IPF fibroblastic focus is a collagen biosynthesis factory embedded in a distinct extracellular matrix

The UIP/IPF fibroblastic focus is a collagen biosynthesis factory embedded in a distinct extracellular matrix

Mathematical models of developmental vascular remodelling: A review

Endothelial cell dysfunction in cardiac disease: driver or consequence?

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