The growth factor progranulin (PGRN) regulates cell division, survival, and migration. PGRN is an extracellular glycoprotein bearing multiple copies of the cysteine-rich granulin motif. With PGRN family members in plants and slime mold, it represents one of the most ancient of the extracellular regulatory proteins still extant in modern animals. PRGN has multiple biological roles. It contributes to the regulation of early embryogenesis, to adult tissue repair and inflammation. Elevated PGRN levels often occur in cancers, and PGRN immunotherapy inhibits the growth of hepatic cancer xenografts in mice. Recent studies have demonstrated roles for PGRN in neurobiology. An autosomal dominant mutation in GRN, the gene for PGRN, leads to neuronal atrophy in the frontal and temporal lobes, resulting in the disease frontotemporal lobar dementia. In this review we will discuss current knowledge of the multifaceted biology of PGRN.

The granulin gene family: from cancer to dementia.

https://www.termis.org/docs/eu10_abstracts/TERMIS2010_0064.pdf

Controlling dispersion of axonal regeneration using a multichannel collagen nerve conduit

Progranulin: a growth factor, a novel TNFR ligand and a drug target.

Mutation of human GRN, the gene encoding the secreted glycoprotein progranulin, results in a form of frontotemporal lobar degeneration that is characterized by the presence of ubiquitinated inclusions containing phosphorylated and cleaved fragments of the transactivation response element DNA-binding protein-43. This has stimulated interest in understanding the role of progranulin in the central nervous system, and in particular, how this relates to neurodegeneration. Progranulin has many roles outside the brain, including regulation of cellular proliferation, survival, and migration, in cancer, including cancers of the brain, in wound repair, and inflammation. It often acts through the extracellular signal-regulated kinase and phopshatidylinositol-3-kinases pathways. The neurobiology of progranulin has followed a similar pattern with proposed roles for progranulin (PGRN) in the central nervous system as a neuroprotective agent and in neuroinflammation. Here we review the structure, biology, and mechanism of progranulin action. By understanding PGRN in a wider context, we may be better able to delineate its roles in the normal brain and in neurodegenerative disease.

Structure, Function, and Mechanism of Progranulin; the Brain and Beyond

Photo-crosslinked poly(ε-caprolactone fumarate) networks for guided peripheral nerve regeneration: Material properties and preliminary biological evaluations

Ankle motion analysis may provide a better method to assess function in the rat sciatic nerve model than the standard method, the sciatic functional index (SFI), but it is not widely used in experiments on nerve regeneration possibly because of complicated analysis. In this study, we investigated the practical use of a two-dimensional (2D) digital video motion analysis system. Reproducibility was investigated in normal rats. Recovery of ankle motion was analyzed after sciatic, tibial, and peroneal nerve crush injury. Results were compared with scores for the SFI. Results were not significantly different from animal-to-animal and day-to-day. Interobserver variability also was small. In the analysis of recovery after separate nerve crush injuries, subtle differences in ankle plantar flexion and dorsiflexion could be detected. The method was also more sensitive than the SFI: whereas scores for the SFI had returned to normal 4 weeks after sciatic nerve crush injury, the ankle angle at mid-stance was still significantly different from that in sham-operated animals 6 weeks after the injury. 2D digital video ankle motion analysis is a practical and sensitive method to assess function in the rat sciatic nerve model.

Two-dimensional digital video ankle motion analysis for assessment of function in the rat sciatic nerve model.

2-D Digital Video Ankle Motion Analysis as Evaluation Method for Functional Recovery in the Rat Sciatic Nerve Model

The granulin-epithelin precursor (GEP/PCDGF), a 68-88 kDa secreted glycoprotein, has been shown to be an important growth and survival factor for ovarian cancer cells. Furthermore, GEP expression is a predictor of patient survival in metastatic ovarian cancer cells. Up to this point, however, the molecular mechanisms and clinical relevance of a GEP-mediated prosurvival phenotype remain poorly characterized. We hypothesize that the prosurvival function of GEP is important in ovarian cancer tumor progression and chemoresponse. To explore this hypothesis, we examined the effects of GEP overexpression on migration, invasion and cisplatin (CDDP) chemosensitivity in the ovarian cancer cell line A2780. Full length GEP transfectants demonstrated an increased capacity to migrate and invade their substratum when compared to empty vector controls. In addition, GEP overexpression was associated with CDDP chemoresistance. Finally, GEP overexpression increased tumor formation and protected cells from tumor regression in response to CDDP treatment in vivo. Taken together, these data support a role for GEP in tumor progression and development of drug resistance.

Prosurvival function of the granulin-epithelin precursor is important in tumor progression and chemoresponse

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Two-dimensional digital video ankle motion analysis for assessment of function in the rat sciatic nerve model.

2-D Digital Video Ankle Motion Analysis as Evaluation Method for Functional Recovery in the Rat Sciatic Nerve Model

Prosurvival function of the granulin-epithelin precursor is important in tumor progression and chemoresponse