The role of progranulin in diabetes and kidney disease

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.

Serum progranulin levels are elevated in infertile women with obesity

“…Progranulin is particularly more highly expressed in visceral adipose tissues of morbid-obese, insulin-resistant patients [22,26]. In a research from Brazil, the authors demonstrated that progranulin may be involved in the pathogenesis of obesity and become a target for metabolic disorder prevention or treatment [27]. When taken altogether, this evidence supports that progranulin plays a regulatory role in glucose and energy homeostasis, and it is possible that it may contribute to the progression of metabolic syndrome [28].…”

PGRN Suppresses Inflammation and Promotes Autophagy in Keratinocytes Through the Wnt/β-Catenin Signaling Pathway

“…For instance, it plays a proinflammatory role in obesity, insulin resistance, dyslipidemia, and metabolic syndrome, while it exerts antiinflammatory effects in wound repair, central nervous system arthritis, acute ischemia-reperfusion injury, and psoriasis [30]. However, there is little knowledge about the normal function of PGRN in the inflammatory response of psoriasis.…”

Remodeling adipose tissue inflammasome for type 2 diabetes mellitus treatment: Current perspective and translational strategies

“…On the other hand, progranulin has an established role in obesity‐associated T2DM pathogenesis. Specifically, this cysteine‐rich protein decreases insulin‐mediated glucose uptake, disrupts insulin signal pathway, increases adipocyte autophagy, and promotes monocyte recruitment in adipose tissue as well as IL‐6 secretion from adipocytes . Elevated progranulin levels are present in obesity‐associated T2DM, nonalcoholic fatty liver disease, nephropathy, and retinopathy .…”

“…Elevated progranulin levels are present in obesity‐associated T2DM, nonalcoholic fatty liver disease, nephropathy, and retinopathy . However, despite the proinflammatory role of progranulin in T2DM, it exhibits anti‐inflammatory function in various other disorders including arthritis, psoriasis, wound repair, and acute ischemia–reperfusion injury . Modulation of the adipokine is not being currently investigated for T2DM therapy in a clinical trial.…”