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Involvement of Progranulin and Granulin Expression in Inflammatory Responses after Cerebral Ischemia

1
Department of Applied Biochemistry, Tokyo University of Pharmacy and Life Sciences; Hachioji 192-0392, Japan
2
Laboratory of Pharmacology, School of Pharmacy, Faculty of Pharmacy and Pharmaceutical Sciences, Josai University, Sakado 350-0295, Japan
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(20), 5210; https://doi.org/10.3390/ijms20205210
Received: 10 September 2019 / Revised: 19 October 2019 / Accepted: 19 October 2019 / Published: 21 October 2019
(This article belongs to the Section Molecular Pathology, Diagnostics, and Therapeutics)
Progranulin (PGRN) plays a crucial role in diverse biological processes, including cell proliferation and embryonic development. PGRN can be cleaved by neutrophil elastase to release granulin (GRN). PGRN has been found to inhibit inflammation. Whereas, GRN plays a role as a pro-inflammatory factor. However, the pathophysiological roles of PGRN and GRN, at early stages after cerebral ischemia, have not yet been fully understood. The aim of this study was to obtain further insight into the pathologic roles of PGRN and GRN. We demonstrated that the amount of PGRN was significantly increased in microglial cells after cerebral ischemia in rats and that neutrophil elastase activity was also increased at an early stage after cerebral ischemia, resulting in the production of GRN. The inhibition of neutrophil elastase activity suppressed PGRN cleavage and GRN production, as well as the increase in pro-inflammatory cytokines, after cerebral ischemia. The administration of an elastase inhibitor decreased the number of injured cells and improved the neurological deficits test scores. Our findings suggest that an increase in the activity of elastase to cleave PGRN, and to produce GRN, was involved in an inflammatory response at the early stages after cerebral ischemia, and that inhibition of elastase activity could suppress the progression of cerebral ischemic injury. View Full-Text
Keywords: cerebral ischemia; progranulin; granulin; elastase; inflammatory cytokine; microglia cerebral ischemia; progranulin; granulin; elastase; inflammatory cytokine; microglia
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Horinokita, I.; Hayashi, H.; Oteki, R.; Mizumura, R.; Yamaguchi, T.; Usui, A.; Yuan, B.; Takagi, N. Involvement of Progranulin and Granulin Expression in Inflammatory Responses after Cerebral Ischemia. Int. J. Mol. Sci. 2019, 20, 5210.

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