Associations between RNA-Binding Motif Protein 3, Fibroblast Growth Factor 21, and Clinical Outcome in Patients with Stroke

Abstract

Background: RNA-binding motif protein 3 (RBM3) is a cold-induced marker of good functional outcome of ischemic stroke that is promising as a protective target. Fibroblast growth factor 21 (FGF21) is an obesity- and temperature-related hormone that upregulates the expression of RBM3, which is beneficial as a recombinant treatment and has been tested under different experimental pathological conditions, including stroke. However, the interaction between RBM3 and FGF21 has not yet been tested for clinical stroke conditions. Methods: In a sample of 66 stroke patients, we analyzed the associations between the FGF21 and RBM3 serum concentrations on admission and at 72 h, body weight, maximum temperature during the first 24 h, and the outcome of patients at 3 months. We also analyzed their association with biomarkers of obesity (adiponectin and leptin) and inflammation (interleukin-6 (IL-6) and interleukin (IL-10)). Results: Higher concentrations of FGF21 on admission and RBM3 at 72 h were associated with good outcomes. Serum FGF21 and RBM3 were directly related to body mass index and inversely related to the maximum temperature during the first 24 h. We found a positive association between the FGF21 concentrations in obese patients with leptin and a negative correlation with adiponectin in non-obese participants. Conclusions: This clinical study demonstrates the association between RBM3 and FGF21 levels and the outcome of stroke patients. Although further investigations are required, these data support the pharmacological induction of RBM3 as a promising protective therapy.

Selective intraarterial hypothermia combined with mechanical thrombectomy for acute cerebral infarction based on microcatheter technology: A single-center, randomized, single-blind controlled study

“…Basic studies have confirmed that RBM3 plays a key role in hypothermia-induced neuroprotection, but research data on RBM3 detection from clinical studies are limited ( 17 , 43 – 46 ). Our study found that RBM3 was elevated in the test group and was associated with a good prognosis, which provided convincing evidence for RBM3 as a novel therapeutic target in ischaemic stroke.…”

Chronic Kidney Disease Induces Proarrhythmic Remodeling

“…In particular, CIRP has been identified as an important mediator of systemic inflammatory response to sepsis and has even been shown to potentiate inflammation leading to tissue injury by acting extracellularly as a damage-associated molecular pattern molecule through the TLR4 (toll-like receptor 4)-MD2 (myeloid differentiation factor 2) complex on macrophages. 62 In addition, circulating FGF-21, which increases drastically with worsening uremia, 63 has been implicated alongside β-klotho as a regulator of RBM3 in neuronal cell culture models and clinical studies of stroke, [64][65][66] hinting at a connection between the CKD-associated changes in RBM3 expression reported here and the FGF-Klotho axis, which is currently under study as a mediator of cardiac arrhythmogenesis in CKD. 50,56 Female Sex Plays a Protective Role in the Progression of CKD and Its Cardiac Sequelae Consistent with the sex-specific differences in renal and cardiac dysfunction observed in our study (Figure 6), previous literature in humans and animals has identified an important role for female sex as a protective factor in the progression of renal failure and CKD-associated CV mortality.…”

ASO targeting RBM3 temperature‐controlled poison exon splicing prevents neurodegeneration in vivo

“…Notably, ASOs in Huntington's disease—albeit being directed at reducing total mRNA expression levels—have not been successful in early human trials, for reasons that are not clear (Kingwell, 2021 ). Safety and large animal studies will be needed before RBM3‐inducing ASOs could be trialed in humans, of course, as well as continually exploring alternative means of RBM3 induction (Ávila‐Gómez et al , 2022 ) and reviewing any possible role of RBM3 in tumor growth and protection (Zhou et al , 2017 ). However, in the search for disease‐modifying therapies for Alzheimer's disease and related dementias, induction of the broadly neuroprotective protein RBM3 via ASO delivery to drive its long‐term expression is a compelling therapeutic approach.…”