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SOCS1 Peptidomimetic Alleviates Glomerular Inflammation in MsPGN by Inhibiting Macrophage M1 Polarization

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A Correction to this article was published on 06 September 2023

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Abstract

Mesangial proliferative glomerulonephritis (MsPGN), the most common pathological change in primary glomerulonephritis, is characterized by increased macrophage infiltration into glomeruli, which results in proinflammatory cytokine release. Macrophage infiltration and differentiation are induced by the Janus kinase 2 and signal transducer and activator of the transcription 1 (JAK2/STAT1) pathway. As a suppressor of cytokine signaling 1 (SOCS1) downregulates the immune response by inhibiting the JAK2/STAT1 pathway, we investigated whether a peptide mimicking the SOCS1 kinase inhibitor region, namely, SOCS1 peptidomimetic, protects against nephropathy. Glomerular JAK2/STAT1 pathway activation was synchronized with kidney injury in an MsPGN rat model. Rats treated with the SOCS1 peptidomimetic exhibited reduced pathological glomerular changes and lessened macrophage recruitment. Moreover, in vivo, the phosphorylation of the JAK2/STAT1 pathway was downregulated in infiltrated macrophages of glomeruli. In vitro, the SOCS1 peptidomimetic inhibited macrophage M1 polarization by suppressing JAK2/STAT1 activation. In conclusion, our study demonstrated that the SOCS1 peptidomimetic plays a protective role against pathologic glomerular changes in MsPGN by reducing macrophage infiltration and inhibiting macrophage polarizing to the M1 phenotype. SOCS1 peptidomimetic, therefore, presents a feasible therapeutic strategy to alleviate renal inflammation in MsPGN.

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Author notes

  1. Yinghua Zhao and Fei Peng have contributed equally to this work.

Authors and Affiliations

  1. Department of Nephrology, First Medical Center of Chinese, State Key Laboratory of Kidney Diseases, PLA General Hospital, Nephrology Institute of the Chinese People’s Liberation Army, National Clinical Research Center for Kidney Diseases, Beijing Key Laboratory of Kidney Disease Research, Beijing, 100853, China

    Yinghua Zhao, Fei Peng, Jiayi He, Yilun Qu, Huiming Ni, Lingling Wu & Xiangmei Chen

  2. School of Clinical Medicine, Beijing Tsinghua Changgung Hospital, Tsinghua University, Beijing, China

    Yinghua Zhao

  3. School of Medicine, Nankai University, Tianjin, China

    Fei Peng

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  1. Yinghua Zhao
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Contributions

Yinghua Zhao wrote the main manuscript text. Fei Peng and Lingling Wu edited the main manuscript text. Jiayi He, Huiming Ni, and Yilun Qu validated the experiments. Xiangmei Chen provided project administration. All authors reviewed the manuscript.

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Correspondence to Xiangmei Chen.

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The original online version of this article was revised: The email address of the second corresponding author was not captured in the published version and it should be, wulingling19860328@163.com.

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Zhao, Y., Peng, F., He, J. et al. SOCS1 Peptidomimetic Alleviates Glomerular Inflammation in MsPGN by Inhibiting Macrophage M1 Polarization. Inflammation 46, 2402–2414 (2023). https://doi.org/10.1007/s10753-023-01886-3

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