miR-200 family promotes podocyte differentiation through repression of RSAD2

Abstract

Mature podocytes are highly differentiated cells with several characteristic phenotypic features that are involved in the glomerular filtration function. During kidney development, a series of changes of the morphological characteristics and cellular functions may happen in podocytes. The miR-200 family functions in various biological and pathological processes. But the underlying molecular mechanisms of miR-200 family that functions in podocyte differentiation remain poorly understood. Herein is shown that miR-200a, miR-200b and miR-429 are significantly upregulated during the differentiation of podocytes, with highest upregulation of miR-200a. In these cells, restraint of miR-200 family by RNA interference assay revealed a prominent inhibition of cell differentiation. More intriguingly, miR-200 family directly inhibited the radical S-adenosyl methionine domain-containing protein 2 (RASD2) expression. Moreover, further upregulation of RSAD2 combining with restraint of miR-200 family revealed a promotion of podocyte dedifferentiation and proliferation. In addition, the expression of RSAD2 is consistent with that of in vitro podocyte differentiation in prenatal and postnatal mouse kidney, and significantly down-regulated during the kidney development. Together, these findings indicate that miR-200 family may potentially promote podocyte differentiation through repression of RSAD2 expression. Our data also demonstrate a novel role of the antiviral protein RSAD2 as a regulator in cell differentiation.

Probing the changes in gene expression due to α-crystallin mutations in mouse models of hereditary human cataract

“…For example, in Cryaa -R49C-het mouse lenses, decreased levels of Clic5 , an intracellular chloride channel that stabilizes membrane-actin filament linkages on hair cells, are consistent with a role of α-crystallin in stabilizing actin filaments [ 50 , 51 ]. Similarly, downregulation of the transcription factors Aebp1 and Rsad2 , which are regulators of cell differentiation, suggest that these proteins are likely associated with early changes in cataract development [ 52 , 53 ]. Ddit3 , also known as CHOP, is an ER overload response transcription factor and a proapoptotic gene, was markedly increased in Cryaa -R49C-homo lenses, consistent with prior reports of upregulation of the CHOP protein in adult Cryaa -R49C-homo lenses [ 54 ].…”

The Functions of MicroRNA-200 Family in Ovarian Cancer: Beyond Epithelial-Mesenchymal Transition

“…Table 1 summarizes the results of a myriad of studies, which suggest that miR-200 members play a critical role in the differentiation and proliferation of neurons [8,9,10], podocyte differentiation [11], taste bud formation [12], insulin signaling pathway regulation in the control of fat body and body size [7], and for the hormonal regulation of endometrial stromal decidualization [13,14] during embryo implantation [15]. …”

The antiviral protein viperin regulates chondrogenic differentiation via CXCL10 protein secretion

“…These actions are specifically activated in response to viral infection and it is therefore surprising to find that in a nonviral context viperin is active as a regulator of cellular differentiation. Previously, alterations in viperin expression have been detected during adipogenic differentiation (31) and podocyte differentiation (32). Middle zone articular cartilage chondrocytes express higher amounts of viperin as compared with superficial zone chondrocytes (33), and viperin expression has been described in osteocytes (34).…”