The plant hormone jasmonate inhibits leaf growth by delaying the switch from the mitotic cell cycle to the endoreduplication cycle and maintains the cell in a stand-by mode but ready-to-go after the ...stress.
Phytohormones regulate plant growth from cell division to organ development. Jasmonates (
JAs
) are signaling molecules that have been implicated in stress-induced responses. However, they have also been shown to inhibit plant growth, but the mechanisms are not well understood. The effects of methyl jasmonate (
MeJA
) on leaf growth regulation were investigated in Arabidopsis (
Arabidopsis thaliana
) mutants altered in
JA
synthesis and perception,
allene oxide synthase
and
coi1
-16B (for
coronatine insensitive1
), respectively. We show that
MeJA
inhibits leaf growth through the
JA
receptor
COI1
by reducing both cell number and size. Further investigations using flow cytometry analyses allowed us to evaluate ploidy levels and to monitor cell cycle progression in leaves and cotyledons of Arabidopsis and/or
Nicotiana benthamiana
at different stages of development. Additionally, a novel global transcription profiling analysis involving continuous treatment with
MeJA
was carried out to identify the molecular players whose expression is regulated during leaf development by this hormone and
COI1
. The results of these studies revealed that
MeJA
delays the switch from the mitotic cell cycle to the endoreduplication cycle, which accompanies cell expansion, in a
COI1
-dependent manner and inhibits the mitotic cycle itself, arresting cells in G1 phase prior to the S-phase transition. Significantly, we show that
MeJA
activates critical regulators of endoreduplication and affects the expression of key determinants of DNA replication. Our discoveries also suggest that
MeJA
may contribute to the maintenance of a cellular “stand-by mode” by keeping the expression of ribosomal genes at an elevated level. Finally, we propose a novel model for
MeJA
-regulated
COI1
-dependent leaf growth inhibition.
Background: Acute T-cell mediated rejection (TCMR) is usually indicated by alteration in serum-creatinine measurements when considerable transplant damage has already occurred. There is, therefore, a ...need for non-invasive early detection of immune signals that would precede the onset of rejection, prior to transplant damage. Methods: We examined the RT-qPCR expression of 22 literature-based genes in peripheral blood samples from 248 patients in the Kidney Allograft Immune Biomarkers of Rejection Episodes (KALIBRE) study. To account for post-transplantation changes unrelated to rejection, we generated time-adjusted gene-expression residuals from linear mixed-effects models in stable patients. To select genes, we used penalised logistic regression based on 27 stable patients and 27 rejectors with biopsy-proven T-cell-mediated rejection, fulfilling strict inclusion/exclusion criteria. We validated this signature in i) an independent group of stable patients and patients with concomitant T-cell and antibody-mediated-rejection, ii) patients from an independent study, iii) cross-sectional pre-biopsy samples from non-rejectors and iv) longitudinal follow-up samples covering the first post-transplant year from rejectors, non-rejectors and stable patients. Findings: A parsimonious TCMR-signature (IFNG, IP-10, ITGA4, MARCH8, RORc, SEMA7A, WDR40A) showed cross-validated area-under-ROC curve 0.84 (0.77–0.88) (median, 2.5th–97.5th centile of fifty cross-validation cycles), sensitivity 0.67 (0.59–0.74) and specificity 0.85 (0.75–0.89). The estimated probability of TCMR increased seven weeks prior to the diagnostic biopsy and decreased after treatment. Gene expression in all patients showed pronounced variability, with up to 24% of the longitudinal samples in stable patients being TCMR-signature positive. In patients with borderline changes, up to 40% of pre-biopsy samples were TCMR-signature positive. Interpretation: Molecular marker alterations in blood emerge well ahead of the time of clinically overt TCMR. Monitoring a TCMR-signature in peripheral blood could unravel T-cell-related pro-inflammatory activity and hidden immunological processes. This additional information could support clinical management decisions in cases of patients with stable but poor kidney function or with inconclusive biopsy results.
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