Open AccessPlectin protects podocytes from adriamycin‐induced apoptosis and F‐actin cytoskeletal disruption through the integrin α6β4/ FAK /p38 MAPK pathway
Author(s) -
Ni Yongliang,
Wang Xin,
Yin Xiaoxuan,
Li Yan,
Liu Xigao,
Wang Haixin,
Liu Xiangjv,
Zhang Jun,
Gao Haiqing,
Shi Benkang,
Zhao Shaohua
Publication year - 2018
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.13816
Subject(s) - plectin , podocyte , microbiology and biotechnology , focal adhesion , podocin , cytoskeleton , phosphorylation , actin cytoskeleton , integrin , chemistry , cancer research , intermediate filament , biology , endocrinology , biochemistry , cell , kidney , proteinuria
Podocyte injury is an early pathological change characteristic of various glomerular diseases, and apoptosis and F‐actin cytoskeletal disruption are typical features of podocyte injury. In this study, we found that adriamycin ( ADR ) treatment resulted in typical podocyte injury and repressed plectin expression. Restoring plectin expression protected against ADR ‐induced podocyte injury whereas si RNA ‐mediated plectin silencing produced similar effects as ADR ‐induced podocyte injury, suggesting that plectin plays a key role in preventing podocyte injury. Further analysis showed that plectin repression induced significant integrin α6β4, focal adhesion kinase ( FAK ) and p38 MAPK phosphorylation. Mutating Y1494, a key tyrosine residue in the integrin β4 subunit, blocked FAK and p38 phosphorylation, thereby alleviating podocyte injury. Inhibitor studies demonstrated that FAK Y397 phosphorylation promoted p38 activation, resulting in podocyte apoptosis and F‐actin cytoskeletal disruption. In vivo studies showed that administration of ADR to rats resulted in significantly increased 24‐hour urine protein levels along with decreased plectin expression and activated integrin α6β4, FAK , and p38. Taken together, these findings indicated that plectin protects podocytes from ADR ‐induced apoptosis and F‐actin cytoskeletal disruption by inhibiting integrin α6β4/ FAK /p38 pathway activation and that plectin may be a therapeutic target for podocyte injury‐related glomerular diseases.