2015
DOI: 10.1074/jbc.m115.662635
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Severe Extracellular Matrix Abnormalities and Chondrodysplasia in Mice Lacking Collagen Prolyl 4-Hydroxylase Isoenzyme II in Combination with a Reduced Amount of Isoenzyme I

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Cited by 47 publications
(62 citation statements)
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“…Notably, the chondrodysplasia observed in p4ha1 þ / À ;p4ha2 À / À double mutant mice is not secondary to uncompensated ER stress, but it is most likely due to severe matrix abnormalities. 38 Overall, these findings suggest that, differently from what has been recently suggested by others 16 and from what our own in vitro data imply, 15 C-P4Hs have a minor role downstream of HIF-1a in the developing growth plate. Similarly, C-P4Hs do not mediate HIF1a function as an early differentiation factor in limb bud mesenchyme.…”
Section: Hif-1a and The Fetal Growth Plate: Facts And Challengescontrasting
confidence: 71%
See 1 more Smart Citation
“…Notably, the chondrodysplasia observed in p4ha1 þ / À ;p4ha2 À / À double mutant mice is not secondary to uncompensated ER stress, but it is most likely due to severe matrix abnormalities. 38 Overall, these findings suggest that, differently from what has been recently suggested by others 16 and from what our own in vitro data imply, 15 C-P4Hs have a minor role downstream of HIF-1a in the developing growth plate. Similarly, C-P4Hs do not mediate HIF1a function as an early differentiation factor in limb bud mesenchyme.…”
Section: Hif-1a and The Fetal Growth Plate: Facts And Challengescontrasting
confidence: 71%
“…The global knockout of C-P4H-I is embryonic lethal, whereas mutant mice universally lacking C-P4H-II are alive and well with no obvious phenotypic abnormalities. 38 Consistent with our hypothesis, whereas heterozygous inactivation of both C-P4H-I and C-P4H-II (p4ha1 þ / À ;p4ha2 þ / À ) or homozygous inactivation of C-P4H-II only (p4ha2 À / À ) leads to the formation of virtually normal cartilage, growth plates from mice carrying heterozygous inactivation of C-P4H-I combined to homozygous inactivation of C-P4H-II (p4ha1 þ / À ; p4ha2 À / À ) display an inner cell death phenotype that is reminiscent of what we observed in HIF-1a null growth plates. However, despite an almost 70% decrease of C-P4H enzymatic activity, the inner cell death phenotype observed in the growth plates of p4ha1 þ / À ; p4ha2 À / À double mutant mice is extremely mild and transient; moreover, it virtually disappears postnatally, and it does not affect mouse survival.…”
Section: Hif-1a and The Fetal Growth Plate: Facts And Challengesmentioning
confidence: 99%
“…These findings are important since collagens are primary components of the extracellular matrix of the sclera and the reduced hydroxylation of their fibrils likely lead to the typical deformation of the myopic eye . The importance of P4HA2 in the pathogenesis of myopia is further supported by evidence that its expression is very intense in the mouse eye as demonstrated by our experimental data, while it is almost undetectable in other tissues of both in human and mouse . We first performed expression and localization studies of P4HA2 in mammalian eye where this molecule co‐localizes with collagens.…”
Section: Discussionmentioning
confidence: 59%
“…Although the prolyl 4‐hydroxylase inhibitor DHB showed a similar effect in both WM239 and SKMEL‐28 cell lines, P4HA1 silencing only resulted in minor changes in the cellular behavior of the SKMEL‐28 cells. This may be due to a compensatory effect of the other common prolyl 4‐hydroxylase alpha subunit, P4HA2, which was expressed at a higher level in SKMEL‐28 cells than in WM239 cells, although previous studies have suggested that P4HA1 may largely compensate for the lack of P4HA2 but not vice versa (Aro et al , ; Holster et al , ). Further, in primary melanoma tumor samples (from http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE98349 dataset), P4HA2 was expressed at a lower level than P4HA1, and its mRNA expression was not significantly associated with survival (as analyzed by us), in concert with our data.…”
Section: Discussionmentioning
confidence: 97%