Loss of miR-29a/b1 promotes inflammation and fibrosis in acute pancreatitis

Dey, Shatovisha; Udari, Lata; Riverahernandez, Primavera; Kwon, Jason J.; Willis, Brandon; Easler, Jeffrey J.; Fogel, Evan L.; Pandol, Stephen J.; Kota, Janaiah

doi:10.1172/jci.insight.149539

Cited by 27 publications

(18 citation statements)

References 50 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…35 miR-29 also inhibits the expression of Col1a1 to a variable extent in different tissue/cell types. 33,34,36,43 However, the repressive effect of miR-29 on Col1a1 expression is mild or undetectable in MC3T3 cells, especially during early phases of differentiation. 35 This raised a long-standing question of how Col1a1 evades the repressive effects of miR-29 during osteogenic differentiation.…”

Section: Discussionmentioning

confidence: 99%

“…Importantly, the pathological overexpression of Col I induces fibrosis, and a miR-29 mimic can act as an antifibrotic agent in different tissues by repressing the expression of Col I and other fibrotic proteins. 33,34,36,43 More than one miR-29 mimic is now in clinical trials as investigative next-generation treatments for idiopathic pulmonary fibrosis. 44 However, the anti-fibrotic effects of miR-29 and its impact on Col I expression vary substantially among tissues, 33,34,36,43 suggesting that tissuespecific APA-mediated shortening of the Col1a1 and Col1a2 3′ UTRs might contribute to inhibiting the anti-fibrotic effects of miR-29 in certain tissues.…”

Section: Discussionmentioning

confidence: 99%

“…In fact, the miR-29 family members have been reported to inhibit the expression of Col1a1 with variable efficiency in different tissues. [33][34][35][36] . miRNA sequencing (miR-seq) of small RNAs that were isolated from d14 calli identified miR-29a-3p as one of the 15 most highly expressed miRNAs, generating ∼20 000 counts per million (CPM) (Table S10).…”

Section: Shortening Of the 3′ Utr Enhances Col1a1 And Col1a2 Expressi...mentioning

confidence: 99%

See 2 more Smart Citations

Transcript shortening via alternative polyadenylation promotes gene expression during fracture healing

et al. 2023

View full text Add to dashboard Cite

Maturation of the 3′ end of almost all eukaryotic messenger RNAs (mRNAs) requires cleavage and polyadenylation. Most mammalian mRNAs are polyadenylated at different sites within the last exon, generating alternative polyadenylation (APA) isoforms that have the same coding region but distinct 3′ untranslated regions (UTRs). The 3′UTR contains motifs that regulate mRNA metabolism; thus, changing the 3′UTR length via APA can significantly affect gene expression. Endochondral ossification is a central process in bone healing, but the impact of APA on gene expression during this process is unknown. Here, we report the widespread occurrence of APA, which impacts multiple pathways that are known to participate in bone healing. Importantly, the progression of endochondral ossification involves global 3′UTR shortening, which is coupled with an increased abundance of shortened transcripts relative to other transcripts; these results highlight the role of APA in promoting gene expression during endochondral bone formation. Our mechanistic studies of transcripts that undergo APA in the fracture callus revealed an intricate regulatory network in which APA enhances the expression of the collagen, type I, alpha 1 (Col1a1) and Col1a2 genes, which encode the 2 subunits of the abundantly expressed protein collagen 1. APA exerts this effect by shortening the 3′UTRs of the Col1a1 and Col1a2 mRNAs, thus removing the binding sites of miR-29a-3p, which would otherwise strongly promote the degradation of both transcripts. Taken together, our study is the first to characterize the crucial roles of APA in regulating the 3′UTR landscape and modulating gene expression during fracture healing.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Shortening Of the 3′ Utr Enhances Col1a1 And Col1a2 Expressi...mentioning

confidence: 99%

See 1 more Smart Citation

Transcript shortening via alternative polyadenylation promotes gene expression during fracture healing

et al. 2023

View full text Add to dashboard Cite

show abstract

“…Dey et al studied the effect of miR-29a/b1 cluster on pancreatic injury and regeneration during AP. The pancreatic cell proliferation was delayed in mIR-29a/b1-deficient (KO) mice group, with some tissue edema, which promoted local and systemic inflammatory response, which indicated that when the expression level of miR-29a/b1 decreased, the occurrence of AP was aggravated [45]. It has been reported that hsa-miR-126a-5p can predict the severity of AP, especially since the combined detection of IL-6 and hsa-miR-126-5p has the highest sensitivity and specificity, which can be used to judge the severity of AP [46].…”

Section: Role Of Exosomes In the Diagnosis Of Acute Pancreatitismentioning

confidence: 99%

Progress in Investigating the Role of Exosomes in Acute Pancreatitis

2023

JCMP

View full text Add to dashboard Cite

Acute pancreatitis (AP) is a potentially fatal disease characterized by parenchymal cell inflammation and apoptosis, with severe local or systemic complications and high mortality rates. At present, the therapeutic aspects of AP are mainly anti-inflammatory and anti-apoptotic, but the mechanistic aspects of AP have not been fully elucidated, so identifying novel therapeutic targets and reliable biomarkers are needed. Exosomes is an extracellular vesicle (40mm-160mm) that includes not only lipids and proteins, but also nucleic acids, mainly tiny ribonucleic acid (miRNA) and messenger ribonucleic acid (mRNA), as well as some genomes and mitochondria. Exosomes can act as intercellular messengers by transferring signaling molecules (including proteins, miRNAs, and lipids) to their target cells. At present, the study of exosomes is gradually deepened, and some types of exosomes are constantly identified in living organisms, which are mainly involved in cell apoptosis, differentiation and inflammatory response. The different roles of exosomes lead to changes in the key physiological functions of AP. In this review, we summarize the various exosomes that currently interact closely with AP, as well as the possible directions of exosome-targeted therapy for the disease, which may help to develop potential biomarkers of the disease and new therapeutic targets to provide ideas for clinical and scientific researchers committed to studying AP.

show abstract

“…Dey et al demonstrated that miR-29a/b1 deletion aggravates pancreatic injury and impairs pancreatic regeneration in AP mice, a result that is consistent with the finding that miR-29a/b1 deficiency causes massive infiltration and activation of inflammatory cells such as neutrophils, and promotes the production of cytokines, such as IL-6, IL-10 and TGFβ1. TGFβ1-mediated pancreatic fibrosis is closely related, but the specific regulatory mechanism still needs to be studied in-depth [ 53 ]. The connection between miRNAs and inflammatory cells may effectively interfere with the vicious cycle in AP.…”

Section: Mirnas and Their Role In Ap Progressionmentioning

confidence: 99%

New challenges for microRNAs in acute pancreatitis: progress and treatment

et al. 2022

View full text Add to dashboard Cite

Acute pancreatitis (AP) is a common clinical abdominal emergency, with a high and increasing incidence each year. Severe AP can easily cause systemic inflammatory response syndrome, multiple organ dysfunction and other complications, leading to higher hospitalization rates and mortality. Currently, there is no specific treatment for AP. Thus, we still need to understand the exact AP pathogenesis to effectively cure AP. With the rise of transcriptomics, RNA molecules, such as microRNAs (miRNAs) transcribed from nonprotein-coding regions of biological genomes, have been found to be of great significance in the regulation of gene expression and to be involved in the occurrence and development of many diseases. Increasing evidence has shown that miRNAs, as regulatory RNAs, can regulate pancreatic acinar necrosis and apoptosis and local and systemic inflammation and play an important role in the development and thus potentially the diagnosis and treatment of AP. Therefore, here, the current research on the relationship between miRNAs and AP is reviewed.

show abstract

Loss of miR-29a/b1 promotes inflammation and fibrosis in acute pancreatitis

Cited by 27 publications

References 50 publications

Transcript shortening via alternative polyadenylation promotes gene expression during fracture healing

Transcript shortening via alternative polyadenylation promotes gene expression during fracture healing

Progress in Investigating the Role of Exosomes in Acute Pancreatitis

New challenges for microRNAs in acute pancreatitis: progress and treatment

Contact Info

Product

Resources

About