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Mast cell tryptases and experimental chronic kidney disease

Grant number: 15/11868-7
Support type:Scholarships abroad - Research Internship - Post-doctor
Effective date (Start): October 15, 2015
Effective date (End): October 14, 2016
Field of knowledge:Biological Sciences - Immunology
Principal Investigator:Niels Olsen Saraiva Câmara
Grantee:Lislaine Andrade Wensing
Supervisor abroad: Richard L. Stevens
Home Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Local de pesquisa : University of New South Wales (UNSW), Australia  
Associated to the scholarship:14/06991-1 - Pathogenic role of mast cells in tubulointerstitial fibrosis development in chronic kidney disease, BP.PD

Abstract

Chronic kidney disease (CKD)§ comprises a heterogeneous group of disorders that adversely effects the structure and function of this organ. CKD eventually progresses to end-stage renal disease, thereby requiring dialysis or transplantation. CKD is a worldwide public health problem that imposes a considerable socio-economic burden to our societies. There is compelling evidence that inflammation plays central roles in the development of CKD. Sustained tissue injury leads to the local release of proinflammatory mediators that promote renal infiltration and accumulation and activation of varied immune cells. Mast cells (MCs) are rarely found in the renal interstitium of normal individuals. However, MC accumulation is prominent in kidney biopsies of patients with CKD, and increased numbers of MCs is positively correlated with functional decline of the kidney. Stored in abundance in the secretory granules of mammalian MCs are three closely related tryptases. In mice, they are known as mouse MC protease (mMCP)-6/Tpsb2, mMCP 7/Tpsab1, and transmembrane tryptase/tryptase-y/Prss31. These tryptases can induce other cell types to increase their expression of cytokines and chemokines. They also can induce matrix metalloproteinase expression and activation which, in turn, leads to remodeling of extracellular matrices. In a preliminary study, we discovered that wild-type mice given the tryptase inhibitor APC 366 had diminished renal fibrosis in a model of obstructive nephropathy. We therefore hypothesize that one or more MC tryptases participate in the development of CKD. Targeting of these tryptases therefore may represent a novel therapeutic approach to reduce the progression of kidney fibrosis.

Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
ZHOU, SAIJUN; TANAKA, KUMIKO; O'KEEFFE, MEREDITH; QI, MIAO; EL-ASSAAD, FATIMA; WEAVER, JAMES C.; CHEN, GANG; WEATHERALL, CHRISTOPHER; WANG, YING; GIANNAKOPOULOS, BILL; CHEN, LIMING; YU, DEMINT; HAMILTON, MATTHEW J.; WENSING, LISLAINE A.; STEVENS, RICHARD L.; KRILIS, STEVEN A. CD117(+) Dendritic and Mast Cells Are Dependent on RasGRP4 to Function as Accessory Cells for Optimal Natural Killer Cell-Mediated Responses to Lipopolysaccharide. PLoS One, v. 11, n. 3 MAR 16 2016. Web of Science Citations: 0.

Please report errors in scientific publications list by writing to: cdi@fapesp.br.