The cell membrane repair protein MG53 modulates transcription factor NF-κB signaling to control kidney fibrosis

Li, Haichang; Duann, Pu; Li, Zhong-Guang; Zhou, Xinyu; Ma, Jianjie; Rovin, Brad H.; Lin, Pei‐Hui

doi:10.1016/j.kint.2021.09.027

Cited by 16 publications

(20 citation statements)

References 52 publications

(55 reference statements)

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“…Various mouse models, including unilateral ureteral obstruction and 5/6 nephrectomy, manifest renal fibrosis (18,19). A bolus injection of folic acid provides the classic mouse model for the progression of AKI to RIF (20, 21).…”

Section: Discussionmentioning

confidence: 99%

LNA-anti-miR-150 alleviates renal interstitial fibrosis by reducing pro-inflammatory M1/M2 macrophage polarization

et al. 2022

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Renal interstitial fibrosis (RIF) is a common pathological feature contributing to chronic injury and maladaptive repair following acute kidney injury. Currently, there is no effective therapy for RIF. We have reported that locked nuclear acid (LNA)-anti-miR-150 antagonizes pro-fibrotic pathways in human renal tubular cells by regulating the suppressor of cytokine signal 1 (SOCS1)/Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway. In the present study, we aimed to clarify whether LNA-anti-miR-150 attenuates folic acid-induced RIF mice by regulating this pathway and by reducing pro-inflammatory M1/M2 macrophage polarization. We found that renal miR-150 was upregulated in folic acid-induced RIF mice at day 30 after injection. LNA-anti-miR-150 alleviated the degree of RIF, as shown by periodic acid–Schiff and Masson staining and by the expression of pro-fibrotic proteins, including alpha-smooth muscle actin and fibronectin. In RIF mice, SOCS1 was downregulated, and p-JAK1 and p-STAT1 were upregulated. LNA-anti-miR-150 reversed the changes in renal SOCS1, p-JAK1, and p-STAT1 expression. In addition, renal infiltration of total macrophages, pro-inflammatory M1 and M2 macrophages as well as their secreted cytokines were increased in RIF mice compared to control mice. Importantly, in folic acid-induced RIF mice, LNA-anti-miR-150 attenuated the renal infiltration of total macrophages and pro-inflammatory subsets, including M1 macrophages expressing CD11c and M2 macrophages expressing CD206. We conclude that the anti-renal fibrotic role of LNA-anti-miR-150 in folic acid-induced RIF mice may be mediated by reducing pro-inflammatory M1 and M2 macrophage polarization via the SOCS1/JAK1/STAT1 pathway.

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Section: Discussionmentioning

confidence: 99%

LNA-anti-miR-150 alleviates renal interstitial fibrosis by reducing pro-inflammatory M1/M2 macrophage polarization

et al. 2022

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“…This study not only identified the signalling pathway by which MG53 elicits renal protection, but also recapitulated the work performed by Duann, et al [80], showing in MG53 -/mice undergoing injury by unilateral ureteral obstruction (UUO), mice exhibited significantly higher levels of fibrosis compared to wild type controls. Renal damage following UUO was partially rescued by pre and post treatment with rhMG53 [81].…”

Section: Mitsugumin 53 (Mg53)mentioning

confidence: 95%

“…Mitsugumin 53 (MG53) is a protein first identified in 2005, alternately named TRIM72, as it belongs to the tripartite motif-containing (TRIM) family of proteins [78]. MG53 is highly expressed in striated muscle (cardiac and skeletal), and, to a lesser extent is expressed in lung, kidney, and immune cells [78][79][80][81]. One of the primary functions of MG53 is cell membrane repair following injury via the recruitment of vesicles to the plasma membrane, suppressing inflammation, and stimulating the production of stem cells [78,82,83].…”

Section: Mitsugumin 53 (Mg53)mentioning

confidence: 99%

“…This study also demonstrated application of rhMG53 intravenously is tolerated in larger animal models using rats and dogs, and that rhMG53 is freely filtered by the kidneys, appearing in urine samples within a few hours of treatment. Further work has shown that MG53 can protect against the development of renal fibrosis by inhibiting the NF-Κβ response [81]. Whilst markers of kidney damage appear in relatively young MG53 -/mice, further structural changes such renal macrophage accumulation, and formation of renal fibrosis starts appearing in mice of older age (5-10 months) [81].…”

Section: Mitsugumin 53 (Mg53)mentioning

confidence: 99%

“…Further work has shown that MG53 can protect against the development of renal fibrosis by inhibiting the NF-Κβ response [81]. Whilst markers of kidney damage appear in relatively young MG53 -/mice, further structural changes such renal macrophage accumulation, and formation of renal fibrosis starts appearing in mice of older age (5-10 months) [81]. This study not only identified the signalling pathway by which MG53 elicits renal protection, but also recapitulated the work performed by Duann, et al [80], showing in MG53 -/mice undergoing injury by unilateral ureteral obstruction (UUO), mice exhibited significantly higher levels of fibrosis compared to wild type controls.…”

Section: Mitsugumin 53 (Mg53)mentioning

confidence: 99%

See 2 more Smart Citations

Skeletal Muscle and Kidney Crosstalk in Chronic Kidney Disease

Jenkin

Perry

2022

Cell Physiol Biochem

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The functioning of complex organisms requires a constant and delicate balance of processes both between and within cells, tissues, and organ systems. There is growing appreciation for the role of signalling crosstalk connecting different organ systems of the body, even from tissues traditionally classified as "inert" in terms of their capacity to produce chemical signals that can act on other organ systems. Many of these secreted molecules have been shown to contribute to, or exacerbate, a variety of functions and diseases in other organ systems, even if the two organs are not functionally linked. For example, there is a strong association with skeletal muscle atrophy and dysfunction in patients with chronic kidney disease (CKD). Identification of molecules produced and secreted by skeletal muscle has existed for some time, and there is emerging evidence that skeletal muscle may directly affect kidney function. Conversely, factors produced and secreted by the kidneys in various models of CKD have been shown to contribute to reduced muscle functionality. This review will focus on crosstalk in both directions between skeletal muscle and the kidneys. The emphasis will be on direct interaction between these organs using examples of secreted factors that are produced by the muscle or kidneys (including activin A, myostatin, microRNA's, irisin and mitsugumin 53), often under pathophysiological conditions. Our understanding of how the kidneys and skeletal muscle interact with each other is key to elucidating the pathophysiology processes that drive health and disease.

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MG53: A potential therapeutic target for kidney disease

Shen

Song

et al. 2022

Pharmacology Res & Perspec

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Ensuring cell survival and tissue regeneration by maintaining cellular integrity is important to the pathophysiology of many human diseases, including kidney disease. Mitsugumin 53 (MG53) is a member of the tripartite motif‐containing (TRIM) protein family that plays an essential role in repairing cell membrane injury and improving tissue regeneration. In recent years, an increasing number of studies have demonstrated that MG53 plays a renoprotective role in kidney diseases. Moreover, with the beneficial effects of the recombinant human MG53 (rhMG53) protein in the treatment of kidney diseases in different animal models, rhMG53 shows significant therapeutic potential in kidney disease. In this review, we elucidate the role of MG53 and its molecular mechanism in kidney disease to provide new approaches to the treatment of kidney disease.

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The cell membrane repair protein MG53 modulates transcription factor NF-κB signaling to control kidney fibrosis

Cited by 16 publications

References 52 publications

LNA-anti-miR-150 alleviates renal interstitial fibrosis by reducing pro-inflammatory M1/M2 macrophage polarization

LNA-anti-miR-150 alleviates renal interstitial fibrosis by reducing pro-inflammatory M1/M2 macrophage polarization

Skeletal Muscle and Kidney Crosstalk in Chronic Kidney Disease

MG53: A potential therapeutic target for kidney disease

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