T?RII Regulates the Proliferation of Metanephric Mesenchyme Cells through Six2 In Vitro.

ABSTRACT: The transforming growth factor-? (TGF?) family signaling pathways play an important role in regulatory cellular networks and exert specific effects on developmental programs during embryo development. However, the function of TGF? signaling pathways on the early kidney development remains unclear. In this work, we aim to detect the underlying role of TGF? type II receptor (T?RII) in vitro, which has a similar expression pattern as the crucial regulator Six2 during early kidney development. Firstly, the 5-ethynyl-2'-deoxyuridine (EdU) assay showed knock down of T?RII significantly decreased the proliferation ratio of metanephric mesenchyme (MM) cells. Additionally, real-time Polymerase Chain Reaction (PCR) and Western blot together with immunofluorescence determined that the mRNA and protein levels of Six2 declined after T?RII knock down. Also, Six2 was observed to be able to partially rescue the proliferation phenotype caused by the depletion of T?RII. Moreover, bioinformatics analysis and luciferase assay indicated Smad3 could transcriptionally target Six2. Further, the EdU assay showed that Smad3 could also rescue the inhibition of proliferation caused by the knock down of T?RII. Taken together, these findings delineate the important function of the TGF? signaling pathway in the early development of kidney and T?RII was shown to be able to promote the expression of Six2 through Smad3 mediating transcriptional regulation and in turn activate the proliferation of MM cells.

SUBMITTER: Mao Z 

PROVIDER: S-EPMC5412437 | biostudies-literature | 2017 Apr

REPOSITORIES: biostudies-literature