RRC ID 67136
著者 Miyake Y, Obana M, Nakae T, Yamamoto A, Tanaka S, Maeda M, Okada Y, Fujio Y.
タイトル PKNOX2 regulates myofibroblast functions and tubular cell survival during kidney fibrosis.
ジャーナル Biochem Biophys Res Commun
Abstract The number of patients with chronic kidney disease (CKD) is increasing worldwide. When kidneys are exposed to severe injury, tubular cell death occurs and kidney fibrosis progresses by activating fibroblasts and myofibroblasts (referred to as (myo)fibroblasts), leading to CKD; however, the pathological and molecular mechanisms underlying CKD, including kidney fibrosis, remain obscure. In the present study, we focused on a transcription factor PBX/Knotted Homeobox 2 (PKNOX2) in kidney fibrosis. The transcript and protein expression of PKNOX2 was upregulated in fibrotic kidneys after unilateral ureteral obstruction (UUO). Importantly, immunofluorescence microscopic analysis revealed that the number of PKNOX2-expressing myofibroblasts was increased, whereas the expression of PKNOX2 was decreased in proximal tubular epithelial cells after UUO. In (myo)fibroblasts, PKNOX2 was induced by TGF-β1. Knockdown of PKNOX2 using shRNA lentiviral system reduced the viability of (myo)fibroblasts either in the presence or absence of TGF-β1, accompanied by increased apoptosis. Moreover, PKNOX2 knockdown decreased TGF-β1-induced migration of myofibroblasts and differentiation of fibroblasts into myofibroblasts. Significantly, knockdown of PKNOX2 also decreased the viability and increased apoptosis of tubular epithelial cells. Collectively, PKNOX2 regulates the function of (myo)fibroblasts and the viability of proximal tubular epithelial cells in progression of kidney fibrosis.
巻・号 571
ページ 88-95
公開日 2021-9-24
DOI 10.1016/j.bbrc.2021.07.067
PII S0006-291X(21)01104-9
PMID 34311199
MeSH Animals Cell Survival Cells, Cultured Fibrosis / metabolism* Fibrosis / pathology Homeodomain Proteins / genetics Homeodomain Proteins / metabolism* Kidney Tubules / metabolism* Kidney Tubules / pathology Male Mice Mice, Inbred C57BL Myofibroblasts / metabolism* Myofibroblasts / pathology Transcription Factors / genetics Transcription Factors / metabolism* Ureteral Obstruction / metabolism* Ureteral Obstruction / pathology
IF 2.985
リソース情報
ヒト・動物細胞 NRK49F(RCB0112)