Repression of CMIP transcription by WT1 is relevant to podocyte health

Moktefi, Anissa; Zhang, Shaoyu; Vachin, Pauline; Ory, Virginie; Hénique, Carole; Audard, Vincent; Rücker‐Martin, Catherine; Gouadon, Elodie; Eccles, Michael R.; Schedl, Andreas; Heidet, Laurence; Ollero, Mario; Sahali, Dil; Pawlak, André

doi:10.1016/j.kint.2016.07.016

Cited by 18 publications

(12 citation statements)

References 58 publications

(86 reference statements)

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“…Details of the construction of Cmip lox/lox mice have been previously reported. 17 A triple transgenic mouse strain (CD2-rtTA/TetOn-Cre/CMIP loxP/loxP ) was generated by sequential crossing. We first crossed Cmip lox/lox mice with C.Cg-Tg(tetO-cre)1Jaw/J mice (strain N° 006244) that were purchased from Jackson laboratory (Bar Harbor, ME USA).…”

Section: Methodsmentioning

confidence: 99%

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CMIP is a negative regulator of T cell signaling

Oniszczuk

Sendeyo

Chhuon³

et al. 2019

Cell Mol Immunol

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Upon their interaction with cognate antigen, T cells integrate different extracellular and intracellular signals involving basal and induced protein–protein interactions, as well as the binding of proteins to lipids, which can lead to either cell activation or inhibition. Here, we show that the selective T cell expression of CMIP, a new adapter protein, by targeted transgenesis drives T cells toward a naïve phenotype. We found that CMIP inhibits activation of the Src kinases Fyn and Lck after CD3/CD28 costimulation and the subsequent localization of Fyn and Lck to LRs. Video microscopy analysis showed that CMIP blocks the recruitment of LAT and the lipid raft marker cholera toxin B at the site of TCR engagement. Proteomic analysis identified several protein clusters differentially modulated by CMIP and, notably, Cofilin-1, which is inactivated in CMIP-expressing T cells. Moreover, transgenic T cells exhibited the downregulation of GM3 synthase, a key enzyme involved in the biosynthesis of gangliosides. These results suggest that CMIP negatively impacts proximal signaling and cytoskeletal rearrangement and defines a new mechanism for the negative regulation of T cells that could be a therapeutic target.

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Section: Methodsmentioning

confidence: 99%

“… 15 However, CMIP is scarcely detectable at both the transcript and protein levels in adult tissues under physiological conditions, which is due at least in part to its notable transcriptional repression by NF-kB and WT1, two master transcription factors. 16 , 17 …”

Section: Introductionmentioning

confidence: 99%

CMIP is a negative regulator of T cell signaling

Oniszczuk

Sendeyo

Chhuon³

et al. 2019

Cell Mol Immunol

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“…CMIP (Cmaf-inducing protein) is a recently identified gene that encodes an 86 kDa protein. In physiological situations, CMIP is repressed by both WT1 and NF-kB, two major transcription factors in podocytes, which may account for its low levels or non-detection in normal glomeruli [ 9 , 10 ]. Evidence based on in vitro and in vivo studies suggest that CMIP induces podocyte signaling disorders and inhibits remodeling of cytoskeleton contributing to podocyte damages [ 11 – 15 ].…”

Section: Introductionmentioning

confidence: 99%

Expression of CMIP in podocytes is restricted to specific classes of lupus nephritis

Bouachi¹,

Moktefi

Zhang

et al. 2018

PLoS ONE

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Lupus glomerulopathies are classified into various histological patterns, which probably result from different pathophysiological origins. Podocyte injury can be demonstrated in lupus nephritis but its clinical relevance is far little appreciated and is often masked by proliferative lesions and inflammatory cell infiltrations. Two patterns of podocyte lesions may be considered, either occurring in the context of renal inflammation or reflecting podocyte dysfunction in non-proliferative and non-inflammatory glomerulopathies. This distinction remains elusive since no reliable biomarker discriminates between both entities. CMIP was recently found induced in some glomerular disease but its expression in different lupus nephritis classes has not been investigated. Twenty-four adult patients with lupus nephritis, including non-proliferative (n = 11) and proliferative (n = 13) glomerulopathies were analyzed. Clinical, biological and immunological data were compared with immunomorphological findings. We analyzed by quantitative and qualitative methods the expression of CMIP in different histological classes. We found CMIP abundance selectively increased in podocytes in class II and class V glomerulopathies, while in proliferative forms (class III and class IV), CMIP was rarely detected. CMIP was not expressed in cellular crescents, endothelial cells or mesangial cells. CMIP colocalized with some subsets of B and T cells within glomerular or interstitial mononuclear cell infiltrates but never with macrophages. Hematuria is rarely present in lupus glomerulopathies expressing CMIP. There was no correlation between classical immunological markers and CMIP expression. Thus, CMIP induction in lupus nephritis seems restricted to non-proliferative glomerulopathies and may define a specific pattern of podocyte injury.

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“…The short protein isoform contributes to several biological pathways and the function of the long protein isoform is rarely known. Several reports have demonstrated that CMIP participates in human kidney diseases through regulating behaviors of podocytes [8, 12, 13]. CMIP is also reported to be associated with reading-related behaviors [14, 15], short-term memory, and language-related traits [7, 16].…”

Section: Introductionmentioning

confidence: 99%

CMIP Promotes Proliferation and Metastasis in Human Glioma

Wang

2017

BioMed Research International

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Glioma is one of the most common primary malignant brain tumors and the outcomes are generally poor. The intrinsic mechanisms involved in glioma development and progression remain unclear. Further studies are urgent and necessary. In this study, we have proven that CMIP (C-Maf-inducing protein) promotes cell proliferation and metastasis in A172 cells through knockdown of CMIP and in U251 cells through overexpression of CMIP by using MTT assay, cell colony formation assay, cell migration assay, and cell invasion assay. Furthermore, we discovered that CMIP upregulates MDM2, which is involved in the promoting role of CMIP in human glioma cells. For clinical study, 99 glioma tissues and 59 normal tissues were analyzed. CMIP expression was higher in glioma tissues than in normal tissues. In glioma tissues, CMIP is found to correlate positively with tumor grade but no significant correlation is found with patients' age, gender, or Karnofsky performance score (KPS). Moreover, CMIP also correlates with low relapse-free survival (RFS) rate and overall survival (OS) rate in glioma patients. Therefore, CMIP is oncogenic and could be a potential target for human glioma diagnosis and therapy.

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Repression of CMIP transcription by WT1 is relevant to podocyte health

Cited by 18 publications

References 58 publications

CMIP is a negative regulator of T cell signaling

CMIP is a negative regulator of T cell signaling

Expression of CMIP in podocytes is restricted to specific classes of lupus nephritis

CMIP Promotes Proliferation and Metastasis in Human Glioma

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