Peroxidasin is required for full viability in development and for maintenance of tissue mechanics in adults

Peebles, K. Elkie; LaFever, Kimberly S.; Page-McCaw, Patrick S.; Colon, Selene; Wang, Dan; Stricker, Aubrie M.; Ferrell, Nicholas; Bhave, Gautam; Page-McCaw, Andrea

doi:10.1016/j.matbio.2023.11.005

Cited by 3 publications

(4 citation statements)

References 32 publications

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“…1A, right side). Identical changes to gut muscle shape are observed in animals lacking the Col4 covalent-crosslinking activity of Peroxidasin (Pxn) 10,12,13 , and basement membranes from such animals also have reduced tensile stiffness in the mechanical stretching assay 10,13,14 . Thus, basement membrane stiffness can be inferred from gut muscle shape, visible either as outlined by basement membrane (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…To test the stiffness hypothesis, we altered basement membrane stiffness another way, by inhibiting Pxn crosslinking, known to contribute substantially to basement membrane tensile stiffness 13,14 . Peroxidasin is irreversibly inhibited by Phloroglucinol (PHG), and we previously showed that 100 µm PHG decreases the tensile stiffness (viscoelastic modulus) of adult fly basement membranes by half 13 . PHG-induced decrease in stiffness was evident in the muscle aspect ratio, and even more pronounced with 5 mM PHG (Fig.…”

Section: Piezo Is Required For Basement Membrane Repair and For Col4 ...mentioning

confidence: 99%

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Piezo initiates transient production of collagen IV to repair damaged basement membranes

Stricker,

Hutson,

Page-McCaw

2023

Preprint

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SummaryBasement membranes are sheets of extracellular matrix separating tissue layers and providing mechanical support. Their mechanical properties are determined largely by their most abundant protein, Collagen IV (Col4). Although basement membranes are repaired after damage, little is known about how. To wit, since basement membrane is extracellular it is unknown how damage is detected, and since Col4 is long-lived it is unknown how it is regulated to avoid fibrosis. Using the basement membrane of the adultDrosophilamidgut as a model, we show that repair is distinct from maintenance. In healthy conditions, midgut Col4 originates from the fat body, but after damage, a subpopulation of enteroblasts we term “matrix menders” transiently express Col4, and Col4 from these cells is required for repair. Activation of the mechanosensitive channel Piezo is required for matrix menders to upregulate Col4, and the signal to initiate repair is a reduction in basement membrane stiffness. Our data suggests that mechanical sensitivity may be a general property of Col4-producing cells.Graphical abstract

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Section: Resultsmentioning

confidence: 99%

Section: Piezo Is Required For Basement Membrane Repair and For Col4 ...mentioning

confidence: 99%

Piezo initiates transient production of collagen IV to repair damaged basement membranes

Stricker,

Hutson,

Page-McCaw

2023

Preprint

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“…Recent studies from Davies and colleagues showed that laminin 111 is also a prominent target for tyrosine nitration [ 30 ] and chlorination [ 23 ] catalyzed by neutrophil myeloperoxidase. However, while myeloperoxidase is typically present in extracellular regions during ongoing inflammatory conditions, PXDN is secreted into BM under physiological conditions to mediate collagen IV crosslinks as a normal feature of BM organization and tissue development [ 36 ]. Therefore, our observations of bromination on specific tyrosines in several laminins and in other BM proteins, including collagen IV α2, collagen VI α1, or Tinagl1, even in healthy mouse or human lung tissues, may reflect potentially physiologically relevant post-translational ECM modifications induced by PXDN that may affect BM function.…”

Section: Discussionmentioning

confidence: 99%

Identification of tyrosine brominated extracellular matrix proteins in normal and fibrotic lung tissues

Cruz,

Habibovic,

Dempsey

et al. 2024

Redox Biology

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“…Knockdown of the D. melanogaster ColIVα1 gene results in a strong reduction in the stiffness of the egg chamber BM, which is not observed with laminin, nidogen, or perlecan knockdown [ 113 ]. Reducing the density of covalent sulfilimine crosslinks, which connect the C-terminuses of collagen IV protomers, destabilizes D. melanogaster egg chamber and larval midgut BMs and decreases BM stiffness in the mouse renal tubule [ 89 , 114 , 115 ]. However, other studies have demonstrated that laminin can contribute significantly to BM stability [ 47 ].…”

Section: Biomechanical Aspectsmentioning

confidence: 99%

Basement Membranes, Brittlestar Tendons, and Their Mechanical Adaptability

Wilkie

2024

Biology

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Basement membranes (BMs) are thin layers of extracellular matrix that separate epithelia, endothelia, muscle cells, and nerve cells from adjacent interstitial connective tissue. BMs are ubiquitous in almost all multicellular animals, and their composition is highly conserved across the Metazoa. There is increasing interest in the mechanical functioning of BMs, including the involvement of altered BM stiffness in development and pathology, particularly cancer metastasis, which can be facilitated by BM destabilization. Such BM weakening has been assumed to occur primarily through enzymatic degradation by matrix metalloproteinases. However, emerging evidence indicates that non-enzymatic mechanisms may also contribute. In brittlestars (Echinodermata, Ophiuroidea), the tendons linking the musculature to the endoskeleton consist of extensions of muscle cell BMs. During the process of brittlestar autotomy, in which arms are detached for the purpose of self-defense, muscles break away from the endoskeleton as a consequence of the rapid destabilization and rupture of their BM-derived tendons. This contribution provides a broad overview of current knowledge of the structural organization and biomechanics of non-echinoderm BMs, compares this with the equivalent information on brittlestar tendons, and discusses the possible relationship between the weakening phenomena exhibited by BMs and brittlestar tendons, and the potential translational value of the latter as a model system of BM destabilization.

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Peroxidasin is required for full viability in development and for maintenance of tissue mechanics in adults

Cited by 3 publications

References 32 publications

Piezo initiates transient production of collagen IV to repair damaged basement membranes

Piezo initiates transient production of collagen IV to repair damaged basement membranes

Identification of tyrosine brominated extracellular matrix proteins in normal and fibrotic lung tissues

Basement Membranes, Brittlestar Tendons, and Their Mechanical Adaptability

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