Parathyroid Hormone–Related Protein Contributes to Early Healing of Habu Snake Venom–Induced Glomerulonephritis in Mice

Hochane, Mazène; Raison, Danièle; Coquard, Catherine; Beraud, C; Danilin, Sabrina; Béthry, Audrey; Massfelder, Thierry; Barthelmebs, Mariette

doi:10.1016/j.ajpath.2017.12.012

Cited by 3 publications

(2 citation statements)

References 34 publications

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“…Mesangial cells can respond to multiple external stimuli (such as macromolecular substances, immune complexes and hypoxia) via the proliferative reaction [ 2 , 21 ]. The main pathological feature of MsPGN includes the proliferation and expansion of mesangial cells [ 22 ]. Hence, inhibiting mesangial cell proliferation is one of the main strategies for treating MsPGN.…”

Section: Discussionmentioning

confidence: 99%

Ntrk1 promotes mesangial cell proliferation and inflammation in rat glomerulonephritis model by activating the STAT3 and p38/ERK MAPK signaling pathways

Dong

Tang

2022

BMC Nephrol

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Background Mesangial proliferative glomerulonephritis (MsPGN) accounts for a main cause of chronic kidney disease (CKD), chronic renal failure and uremia. This paper aimed to examine the effect of Ntrk1 on MsPGN development, so as to identify a novel therapeutic target for MsPGN. Methods The MsPGN rat model was constructed by single injection of Thy1.1 monoclonal antibody via the tail vein. Additionally, the Ntrk1 knockdown rat model was established by injection of Ntrk1-RNAi lentivirus via the tail vein. Periodic acid-schiff staining and immunohistochemistry (IHC) were performed on kidney tissues. Moreover, the rat urinary protein was detected. Mesangial cells were transfected and treated with p38 inhibitor (SB202190) and ERK inhibitor (PD98059). Meanwhile, the viability and proliferation of mesangial cells were analyzed by cell counting kit-8 (CCK-8) and 5-Ethynyl-2′-deoxyuridine assays. Gene expression was detected by quantitative real-time polymerase chain reaction (qRT-PCR) and Western-blot (WB) assays. Results The proliferation of mesangial cells was enhanced in glomerulus and Ki67 expression was up-regulated in renal tubule of MsPGN rats. The urine protein level increased in MsPGN rats. Pro-inflammatory factors and Ntrk1 expression were up-regulated in glomerulus of MsPGN rats. Ntrk1 up-regulation promoted the viability, proliferation, expression of pro-inflammatory factors and activation of the STAT3, p38 and ERK signaling pathways in mesangial cells. Ntrk1 knockdown reduced mesangial cell proliferation, urine protein, pro-inflammatory factors, activation of STAT3, p38 and ERK signaling pathways in glomerulus, and decreased Ki67 expression in renal tubule of MsPGN rats. Treatment with SB202190 and PD98059 reversed the effect of Ntrk1 on promoting the viability, proliferation and inflammatory response of mesangial cells. Conclusion Ntrk1 promoted mesangial cell proliferation and inflammation in MsPGN rats by activating the STAT3 and p38/ERK MAPK signaling pathways.

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Section: Discussionmentioning

confidence: 99%

Ntrk1 promotes mesangial cell proliferation and inflammation in rat glomerulonephritis model by activating the STAT3 and p38/ERK MAPK signaling pathways

Dong

Tang

2022

BMC Nephrol

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“…Single caudal injection of HSV can cause the damage to GMCs, which can induce the mesangial proliferative nephritis in various experimental animals, including mouse, becoming one of the well-recognized models for the research of human MsPGN. 22 In the present study, the low dose of HSV (4 mg/kg body weight) was used to establish our experimental model of MsPGN mice since the high dose of HSV (6 mg/kg body weight) was very toxic, which demonstrated the similar MC proliferation to rat Thy-1 glomerulonephritis. 16 Existing data stated that HSV-induced MsPGN models could maintain the disease course within 2-3 weeks, and mesangium dissolution occurs within 1-3 days after HSV injection, followed by the proliferation of MCs and aggregation of and E) Comparison of the cycle distribution among groups; * P < 0.05 versus Blank group and Control activation particles group; # P < 0.05 versus SOCS-3 activation particles group; & P < 0.05 versus Control siRNA group.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of suppressor of cytokine signaling‐3 affects mesangial cell proliferation and cell cycle in mesangioproliferative glomerulonephritis

Liu

Wang

Zhou

2021

The Kaohsiung J of Med Scie

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To explore the role of suppressor of cytokine signaling-3 (SOCS-3) in mesangial proliferative glomerulonephritis (MsPGN). SOCS-3 expression in kidney tissues from MsPGN patients was detected using immunohistochemistry. Double immunofluorescence staining was performed to investigate the localization of SOCS-3 with α-SMA in glomeruli. Heminephrectomized wild-type (WT) and SOCS-3 À/À (KO) mice were injected with Habu-snake venom (HSV) to establish MsPGN models, and renal function were compared. Simultaneously, immunofluorescence, periodic acid-Schiff staining, Picrosirius red staining, as well as immunohistochemistry for PCNA, MAC-2 and type IV collagen in glomeruli were performed. In addition, primary mouse renal mesangial cells and SV40 MES-13 cells were transfected with SOCS-3 siRNA or SOCS-3 lentiviral activation particles, followed by EdU assay, flow cytometry, quantitative reverse transcription-polymerase chain reaction, and Western blotting. Mesangial SOCS-3 expression was enhanced in glomeruli of MsPGN patients, and SOCS-3 was well colocalized with activated α-SMA. After HSV injection, WT and KO mice presented with the increases in the serum creatinine, urea nitrogen, and urinary protein, especially in KO mice. Besides, SOCS-3 À/À alleviated the hyperplasia of glomerular MCs in MsPGN mice, with the reductions in PCNA, MAC-2, and collagen deposition. Furthermore, SOCS-3 inhibition reduced the cell proportion at S phase to suppress cell proliferation, with the downregulations of Cyclin A, Cyclin D1, PCNA, and Ki-67. SOCS-3 knockout can alleviate the hyperplasia of glomerular MCs in MsPGN mice via affecting the cell cycle and proliferation of MCs, thus being a potential therapeutic target for MsPGN.

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Hypercalcemia Secondary to Elevated PTHrP in an Infant Followed by Progression to Nephrotic Syndrome

Gimeno,

Hunley,

Kelley

2024

JCEM Case Reports

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In infants, hypercalcemia from elevated parathyroid hormone-related protein (PTHrP) is rare, often signaling neoplasm or renal or urinary anomalies. We report an infant who presented with failure to thrive and hypercalcemia at 10 months old, with initial evaluation showing elevated PTHrP of unclear etiology with imaging negative for neoplasm and no structural anomalies of the kidneys or ureters on ultrasound. Within 6 months of presentation, the patient developed nephrotic syndrome and by 2 years had progressed to end-stage kidney disease, necessitating kidney transplantation. Genetic testing was inconclusive but suggested congenital nephrotic syndrome. While reports of hypercalcemia secondary to elevated PTHrP exist in children with known structural renal anomalies, this is the first to demonstrate hypercalcemia and PTHrP elevation before detection of renal abnormalities. Experimental models have suggested a role for increased PTHrP expression in renal cells following acute kidney injury from nephrotic syndrome, and clinically detectable PTHrP levels may indicate progression of renal injury. We suggest monitoring of renal function for early detection of nephrotic syndrome in infants and children with elevated PTHrP who otherwise lack anatomical renal anomalies or detectable malignancies.

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Parathyroid Hormone–Related Protein Contributes to Early Healing of Habu Snake Venom–Induced Glomerulonephritis in Mice

Cited by 3 publications

References 34 publications

Ntrk1 promotes mesangial cell proliferation and inflammation in rat glomerulonephritis model by activating the STAT3 and p38/ERK MAPK signaling pathways

Ntrk1 promotes mesangial cell proliferation and inflammation in rat glomerulonephritis model by activating the STAT3 and p38/ERK MAPK signaling pathways

Inhibition of suppressor of cytokine signaling‐3 affects mesangial cell proliferation and cell cycle in mesangioproliferative glomerulonephritis

Hypercalcemia Secondary to Elevated PTHrP in an Infant Followed by Progression to Nephrotic Syndrome

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