BMP7 dose-dependently stimulates proliferation and cadherin-11 expression via ERK and p38 in a murine metanephric mesenchymal cell line

Abstract

BMP7 is expressed in ureteric buds and cap mesenchyme of the fetal kidney, mediating branching morphogenesis and survival and priming of metanephric mesenchyme. Although dose‐dependent effects of BMP7 in collecting duct cells have been reported, studies in metanephric mesenchymal cells are lacking. We examined the effects of BMP7 on MAP kinase activation, proliferation, and expression of cadherins in a metanephric mesenchymal cell line MS7 by thymidine incorporation, immunoblot analysis, and quantitative real‐time PCR. The levels of phosphorylated ERK (P‐ERK) and phosphorylated p38 (P‐p38) were not altered at 10 min, 1 h, and 6 h with low‐dose BMP7 (0.25 nmol/L), but were increased at 24 h. At 24 h, P‐ERK was increased with low‐dose BMP7, but not by intermediate‐ (1 nmol/L) or high‐dose (10 nmol/L) BMP7, whereas p38 was activated by intermediate‐dose BMP7. Cell proliferation of MS7 was significantly increased by low‐ and intermediate‐dose BMP7 and decreased by high‐dose BMP7. A p38 inhibitor SB203580 5 μmol/L or a MEK inhibitor PD98059 5 μmol/L abolished BMP7‐stimulated proliferation. Expression of cadherin‐11, an adhesion molecule known to promote cell migration and compaction, was upregulated by intermediate‐dose BMP7. BMP7‐induced cadherin‐11 expression was inhibited by cotreatment with SB203580 and PD98059. Finally, in metanephroi cultured with siRNA for cadherin‐11, the number and thickness of cap mesenchyme were reduced. In conclusion, BMP7 exerts differential effects depending on the concentration; it may expand mesenchymal cells in the stroma where BMP7 concentration is low and may upregulate cadherin‐11 promoting condensation around the tip of ureteric buds.

Bone morphogenetic protein 7 promotes resistance to immunotherapy

“…Our studies revealed that proteins known to be related to BMP7 signaling, such as MAPK14 24,25,[34][35][36][37] , were expressed differently in resistant tumors than in parental tumors. Because MAPK14 is known to be regulated by BMP7 23,24 via SMAD activation 25 , we focused on this protein for validation studies.…”

“…Because MAPK14 is known to be regulated by BMP7 23,24 via SMAD activation 25 , we focused on this protein for validation studies. BMP7 can either promote or inhibit MAPK14 activation depending on the cellular context and BMP7 dose [23][24][25]36 . Here, we found that BMP7 specifically regulated MAPK14 at the mRNA and protein levels.…”

Classification of Widely and Rarely Expressed Genes with Recurrent Neural Network

“…The next GO term describes a quite significant biological process, the regulation of metanephric cap mesenchymal cell proliferation ( GO:0090095 ). As a tissue specific biological process, the involvement of this GO term in various tumor associated genes, such a cadherin family, p38, and MYC, has been confirmed [ 84 , 85 ] In cancers, particularly renal carcinoma, genes that contribute to GO:0090095 have been reported to be up-regulated compared with other irrelevant genes [ 86 ], thereby conforming to the expression profile clustering function of such a GO term. GO:0004872 , which describes the general receptor activity, may have also been enriched by genes with high or low expression patterns.…”

Diffuse midline glioma invasion and metastasis rely on cell-autonomous signaling

“…BMP7 was previously reported as an activator of the non-canonical BMP effectors MEK and ERK kinases. 35 , 36 MEK- and ERK-signaling pathways were shown to regulate normal OPC migration. 37 , 38 As expected, exogenous rBMP7 rapidly activated the phosphorylation of canonical BMP signaling effectors SMAD1/5/9 in both poorly- and highly invasive models ( Figure 6A ).…”