The role of progranulin in diabetes and kidney disease.

Bruna Bellincanta Nicoletto,Luis Henrique Canani

doi:10.1186/s13098-015-0112-6

Bruna Bellincanta Nicoletto, Luis Henrique Canani

Open Access

https://doi.org/10.1186/s13098-015-0112-6

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Abstract

Progranulin (PGRN) is a cysteine rich secreted protein, expressed in epithelial cells, immune cells, neurons, and adipocytes. It was first identified for its growth factor-like properties, being involved in early embryogenesis and tissue remodeling, acting as an anti-inflammatory molecule. In the central nervous system, PGRN has neurotrophic and neuroprotective actions. There is also evidence of PGRN effects on cancer, contributing to tumor proliferation, invasion and cell survival. Recently, PGRN was recognized as an adipokine related to obesity and insulin resistance, revealing its metabolic function and pro-inflammatory properties. In obesity and type 2 diabetes mellitus, PGRN levels are increased. In renal disease, there is a relevant association, however, it is not known if it could contribute to kidney damage or if it is only a route of PGRN elimination. PGRN is an emerging molecule which demands studies in different fields. Possibly, it plays distinct functions in different tissues/cells and metabolic conditions. Here, we discuss potential mechanisms and recent data of PGRN pro-inflammatory actions, regarding obesity, insulin resistance, type 2 diabetes mellitus and kidney disease.

Highlights

Progranulin (PGRN) is a 68–88 kDa cysteine rich secreted protein, known as granulin-epithelin precursor, proepithelin or PC-cell derived growth factor [1, 2]
Type 2 diabetes mellitus and PGRN From 1988 to 2010, the total number of persons with diabetes increased by almost 75 % [50]
It was previously demonstrated that expression of PGRN in intact skin is low, but in injured skin, it raises significantly [1]

Summary

Background

Progranulin (PGRN) is a 68–88 kDa cysteine rich secreted protein, known as granulin-epithelin precursor, proepithelin or PC-cell derived growth factor [1, 2]. In ob/ob mice, a well-characterized obese and insulin resistance model, there are elevated PGRN serum levels and upregulation of Grn in white adipose tissue [35]. Body weight, fat mass and size of adipocytes were lower in Grn deficient mice compared to the wildtype mice receiving a standard diet [35] A recent study evaluating T2DM patients reports that obese subjects present higher levels of PGRN [30]. In a recent study evaluating eighty-four T2DM patients, increased PGRN serum levels were described in macroalbuminuric subjects [75].

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