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BIGH3: A New Target in Diabetic Complications
Author(s) -
CastanedaGill Jessica Marguerite,
Hardikar Swanand,
Navarro Mary,
Kotchan Eileen,
Kim Hong S.,
Zhao Qingwei,
Lee Chi F.,
Tsin Andrew,
Asmis Reto,
LeBaron Richard
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.530.4
Subject(s) - medicine
The extracellular matrix molecule TGFβ‐Induced Gene Human Clone 3 (BIGH3) is a proapoptotic protein that is upregulated by TGFβ. BIGH3 expression was increased 10‐fold in type 2 diabetic human kidney cortex compared to similarly‐aged healthy kidney cortex. We also detected elevated levels of secreted BIGH3 in tissues from diabetic mice, including eye, kidney, and the vasculature. Recombinant BIGH3 induced apoptosis in RPTEC and retinal pericytes (RP) through an integrin‐mediated pathway. Activated macrophages are found in diabetic tissues and secrete TGFβ1. We hypothesize that macrophage‐secreted TGFβ1 may account for the increased accumulation of BIGH3 and tissue damage associated with diabetic complications. To test this hypothesis, we treated VSMC, RPTEC, retinal EC, and RP with conditioned medium from human macrophages (MCM) that were incubated either at normal glucose levels or high glucose plus human LDL (diabetic condition). Cells treated with diabetic MCM exhibited increased BIGH3 expression when compared to cells incubated with non‐diabetic MCM. Immunohistochemistry performed on diabetic mice kidney cryosections showed co‐localization of macrophages with BIGH3. We therefore propose that macrophage‐derived TGFβ may be responsible for the increased secretion of BIGH3 and contribute to tissue apoptosis associated with diabetic complications. Funded by NIH/NIGMS GM60655 and SALSI.