The Matricellular Protein Fibulin-5 Regulates β-cell Proliferation in an Autocrine/paracrine Manner

Overview

Journal iScience

Publisher Cell Press

Date 2025 Feb 25

PMID 39995864

Authors

Tomoko Okuyama

Takahiro Tsuno

Ryota Inoue

Setsuko Fukushima

Mayu Kyohara

Anzu Matsumura

Daisuke Miyashita

Kuniyuki Nishiyama

Yusuke Takano

Yu Togashi

Makiko Meguro-Horike

Shin-Ichi Horike

Tatsuya Kin

A M James Shapiro

Hiromi Yanagisawa

Yasuo Terauchi

Jun Shirakawa

Affiliations

Soon will be listed here.

Abstract

The matricellular protein Fibulin-5 (Fbln5) is a secreted protein that is essential for elastic fiber formation, and pancreatic islets are usually surrounded by the extracellular matrix (ECM), which includes elastic fibers. However, much uncertainty remains regarding the function of the ECM and its components in β-cells. Here, we describe the role of Fbln5 in β-cell replication. Fbln5 expression was increased upon glucose stimulation in β-cells of mouse and human islets. β-Cell-specific -knockout (βKO) mice exhibit significantly reduced β-cell proliferation but not . Secreted extracellular Fbln5 enhances β-cell replication. -deficient β-cells exhibit the downregulated expression of the gene encoding Polo-like kinase 1 (PLK1), which is accompanied by ERK-mediated FoxM1 nuclear export. These data suggest that Fbln5 is secreted from β-cells in response to glucose and plays important roles in the appropriate maintenance of β-cell functions in an autocrine or paracrine manner.

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