Interference with miR-210 Alleviated Renal Injury in Septic Rats by Inhibiting JAK-STAT Pathway

Zhang, Benchao; Guo, Zhang; Lai, Siqi; Chen, Hongjian

doi:10.1007/s10753-020-01283-0

Cited by 21 publications

(13 citation statements)

References 18 publications

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“…In contrary, another hypertrophy-related miR, miR-210, showed no correlation with miR-181a neither in healthy, nor in OA cartilage tissue. This miR has been earlier implicated to regulation of NF-κB (Ren et al, 2017) and JAK/STAT (Zhang et al, 2020) and WNT (Li et al, 2019), with no evidence for effects on BMP signaling. Collectively, these data indicate that miR-181a regulates the balance between two major signaling pathways, WNT-BMP which define the chondral versus endochondral development in cartilage tissue (Figure 7).…”

Section: Mir-181a Inhibited Erk1/2 Phosphorylation In Mesenchymal Stromal Cells Chondrogenesismentioning

confidence: 88%

MiR-181a Targets RSPO2 and Regulates Bone Morphogenetic Protein – WNT Signaling Crosstalk During Chondrogenic Differentiation of Mesenchymal Stromal Cells

Melnik

Hofmann

Gabler

et al. 2021

Front. Cell Dev. Biol.

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Mechanisms of WNT and bone morphogenetic protein (BMP) signaling crosstalk is in the focus of multiple biological studies, and it also has been discovered to play important roles in human mesenchymal stromal cells (MSC) that are of great interest for neocartilage engineering due to their high chondrogenic differentiation potential. However, MSC-derived chondrocytes undergo hypertrophic degeneration that impedes their clinical application for cartilage regeneration. In our previous study, we established that several microRNAs (miRs) are differentially expressed between articular chondrocytes (AC) – and MSC-derived neocartilage, with miR-181a being the most prominent candidate as key microRNA involved in the regulation of a balance between chondral and endochondral differentiation. The aim of this study was the identification of precise mRNA targets and signaling pathways regulated by miR-181a in MSC during chondrogenesis. MiR-181a was upregulated during chondrogenesis of MSC, along with an increase of the hypertrophic phenotype in resulting cartilaginous tissue. By in silico analysis combined with miR reporter assay, the WNT signaling activator and BMP signaling repressor RSPO2 was suggested as a target of miR-181a. Further validation experiments confirmed that miR-181a targets RSPO2 mRNA in MSC. It was found that in human MSC miR-181a activated BMP signaling manifested by the accumulation of SOX9 protein and increased phosphorylation of SMAD1/5/9. These effects, together with the concomitant reduction of canonical WNT signaling induced by miR-181a mimic, were in accordance with the effects expected by the loss of RSPO2, thus indicating the causative link between miR-181a and RSPO2. Moreover, we observed that a tight correlation between miR-181a and miR-218 expression levels in healthy human cartilage tissue was disrupted in osteoarthritis (OA) highlighting the importance of the WNT-BMP signaling crosstalk for preventing OA.

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Section: Mir-181a Inhibited Erk1/2 Phosphorylation In Mesenchymal Stromal Cells Chondrogenesismentioning

confidence: 88%

MiR-181a Targets RSPO2 and Regulates Bone Morphogenetic Protein – WNT Signaling Crosstalk During Chondrogenic Differentiation of Mesenchymal Stromal Cells

Melnik

Hofmann

Gabler

et al. 2021

Front. Cell Dev. Biol.

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“…STAT3 pathway in septic AKI rats is significantly activated, while inhibition of STAT3 has displayed remarkable protective effects on septic AKI in mice (B. Zhang et al, 2020). Curcumin ameliorates CLP-induced AKI through reducing inflammation and cell apoptosis and suppressing JAK2/STAT3…”

Section: Kidney Failurementioning

confidence: 99%

Targeting STAT3: A crucial modulator of sepsis

Lei

Liu

Sun

et al. 2021

Journal Cellular Physiology

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Signal transducer and activator of transcription 3 (STAT3) is a cellular signal transcription factor that has recently attracted a great deal of attention. It can trigger a variety of genes transcription in response to cytokines and growth factors stimulation, which plays an important role in many cellular biological processes involved in anti/proinflammatory responses. Sepsis is a life-threatening organ dysfunction resulting from dysregulated host responses to infection. As a converging point of multiple inflammatory responses pathways, accumulating studies have presented the elaborate network of STAT3 in sepsis pathophysiology; these results generally indicate a promising therapeutic application for targeting STAT3 in the treatment of sepsis. In the present review, we evaluated the published literature describing the use of STAT3 in the treatment of experimental and clinical sepsis. The information presented here may be useful for the design of future studies and may highlight the potential of STAT3 as a future biomarker and therapeutic target for sepsis.

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“…However, increased cleaved-caspase 3 and decreased Bcl-2 expressions were detected in CLPAKI mice with BBL. Previous study also found cleaved-caspase 3 was increased in CLP rat with tubular injury ( 17 ).…”

Section: Discussionmentioning

confidence: 55%

“…Comparing the data from early-stage SIAKI mice and AKI patients, we found that early-stage SIAKI in CLP mice had similar biochemical and renal histopathological features to AKI patients. Many previous studies have used acute renal failure animal models for preventing the progression of AKI to chronic kidney disease ( 10 , 17 , 18 , 23 – 26 ), but few have used early-stage AKI model for inhibiting the occurrence and development of AKI. Current management of AKI, a potentially fatal disorder in sepsis patients, is merely supportive.…”

Section: Discussionmentioning

confidence: 99%

ACE2 Promoted by STAT3 Activation Has a Protective Role in Early-Stage Acute Kidney Injury of Murine Sepsis

Chen

Fang²,

Zhu³

et al. 2022

Front. Med.

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Sepsis-induced AKI (SIAKI) is the most common complication with unacceptable mortality in hospitalized and critically ill patients. The pathophysiology of the development of SIAKI is still poorly understood. Our recent work has demonstrated the role of signal transducer and activator of transcription 3 (STAT3) pathways in regulating inflammation and coagulation in sepsis. We hypothesized that STAT3 activation has a critical role in early-stage SIAKI. The early-stage SIAKI model was established in cecal ligation and puncture (CLP) mice, which recapitulates the clinical and renal pathological features of early-stage AKI patients. Brush border loss (BBL) was the specific pathological feature of acute tubular injury in early-stage AKI. The role of STAT3 signaling and angiotension system in early-stage SIAKI was evaluated. The STAT3 activation (increased pSTAT3) and increased angiotensin-converting enzyme 2 (ACE2) expressions were observed in CLP mice. The low responsive expressions of pSTAT3 and ACE2 to septic inflammation in CLP AKI mice were associated with BBL. Correlation analysis of proteins' expressions showed pSTAT3 expression was significantly positively related to ACE2 expression in CLP mice. Reduced pSTAT3 after S3I201 intervention, which blocked STAT3 phosphorylation, decreased ACE2 expression, and exacerbated tubular injury in early-stage SIAKI. Our data indicate that endogenous increase of ACE2 expression upregulated by STAT3 activation in early-stage SIAKI play protective role against acute tubular injury.

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Interference with miR-210 Alleviated Renal Injury in Septic Rats by Inhibiting JAK-STAT Pathway

Cited by 21 publications

References 18 publications

MiR-181a Targets RSPO2 and Regulates Bone Morphogenetic Protein – WNT Signaling Crosstalk During Chondrogenic Differentiation of Mesenchymal Stromal Cells

MiR-181a Targets RSPO2 and Regulates Bone Morphogenetic Protein – WNT Signaling Crosstalk During Chondrogenic Differentiation of Mesenchymal Stromal Cells

Targeting STAT3: A crucial modulator of sepsis

ACE2 Promoted by STAT3 Activation Has a Protective Role in Early-Stage Acute Kidney Injury of Murine Sepsis

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