Skip to Content
Merck
  • Differential Roles of Cysteinyl Cathepsins in TGF-β Signaling and Tissue Fibrosis.

Differential Roles of Cysteinyl Cathepsins in TGF-β Signaling and Tissue Fibrosis.

iScience (2019-08-26)
Xian Zhang, Yi Zhou, Xueqing Yu, Qin Huang, Wenqian Fang, Jie Li, Joseph V Bonventre, Galina K Sukhova, Peter Libby, Guo-Ping Shi
ABSTRACT

Transforming growth factor beta (TGF-β) signaling contributes to tissue fibrosis. Here we demonstrate that TGF-β enhances CatS and CatK expression but reduces CatB and CatL expression in mouse kidney tubular epithelial cells (TECs). CatS- and CatK deficiency reduces TEC nuclear membrane importer importin-β expression, Smad-2/3 activation, and extracellular matrix (ECM) production. Yet CatB- and CatL-deficiency displays the opposite observations with reduced nuclear membrane exporter RanBP3 expression. CatS and CatK form immunocomplexes with the importin-β and RanBP3 more effectively than do CatB and CatL. On the plasma membrane, CatS and CatK preferentially form immunocomplexes with and activate TGF-β receptor-2, whereas CatB and CatL form immunocomplexes with and inactivate TGF-β receptor-1. Unilateral ureteral obstruction-induced renal injury tests differential cathepsin activities in TGF-β signaling and tissue fibrosis. CatB- or CatL-deficiency exacerbates fibrosis, whereas CatS- or CatK-deficiency protects kidneys from fibrosis. These cathepsins exert different effects in the TGF-β signaling cascade independent of their proteolytic properties.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Monoclonal Anti-Actin, α-Smooth Muscle, clone 1A4, ascites fluid
SKU
Pack Size
Availability
Price
Quantity
Sigma-Aldrich
ApopTag Peroxidase In Situ Apoptosis Detection Kit, The ApopTag Peroxidase In Situ Apoptosis Detection Kit detects apoptotic cells in situ by labeling & detecting DNA strand breaks by the TUNEL method.
SKU
Pack Size
Availability
Price
Quantity