Jason Shenoi

1. Introduction: Kidney disease is a progressive disease affecting more than 37 million Americans. It is classified as the consequence of chronic infection, obstruction, or hypertension with the deposition of collagen, extracellular matrix (ECM), and fibrogenesis.¹ To reduce the effects of kidney disease and circumvent the need for transplants, the compound Bone Morphogenic Protein (BMP) 7 can be used to reverse the epithelial to mesenchymal transition of cells, decreasing the rates of renal fibrosis, ECM, and collagen deposition. A basic understanding of the use of BMP7 is understood, but its mechanistic actions remain largely unknown.² Methods: Most pathways were tested on Unilateral Ureteral Obstructed mice. For each pathway tested, genes were transfected to ensure production of a specific factor with a relationship to BMP7 along with the precursor to BMP7.⁴ Pathways: MiRNA-21, an important factor in the deposition of collagen III and a-smooth muscle actin, was seen to decrease with the addition of BMP7. SMAD was also seen to be a stimulant for the production and deposition of ECM and fibrogenesis which was seen to decrease with the addition of BMP7.³ Akt phosphorylation, instrumental in the deposition of collagen, was found to be halted by the addition of BMP7. This inhibition resulted in the upregulation of PTEN, a gene involved in the inhibition of fibroblast proliferation and migration.⁴ Chlorogenic Acid was found to be a stimulant of BMP7 as an inducible factor along with Hepatic Growth factor for stimulating kidney repair.⁵ The Ski-related novel Protein N (SnoN) was found to be correlated with renal fibrosis and inducible for kidney repair. BMP7 was found to increase mRNA production of SnoN to revert present fibrosis.⁶ Conclusions: A basic understanding of each of these pathways demonstrates BMP7s role in the regulation of renal fibrosis, while an in-depth understanding of these mechanisms are yet to be fully understood, BMP7 therapeutic research is still in development. Adenovirus cell targeting is currently being used to create overexpression of BMP7 in specific cells. BMP7 is also known to have systemic effects in its use as a neuroprotective element along with other organ systems. With its decrease in fibrosis and increase in epithelial proliferation, it is correlated with a higher incidence of cancer.⁷ Long term effects are still being studied in BMP7’s role in renal protection and its therapeutic effects.

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