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World J Stem Cells. Sep 26, 2016; 8(9): 288-296
Published online Sep 26, 2016. doi: 10.4252/wjsc.v8.i9.288
Roles and regulation of bone morphogenetic protein-7 in kidney development and diseases
Taro Tsujimura, Mana Idei, Masahiro Yoshikawa, Osamu Takase, Keiichi Hishikawa
Taro Tsujimura, Mana Idei, Masahiro Yoshikawa, Osamu Takase, Keiichi Hishikawa, Department of Advanced Nephrology and Regenerative Medicine, Division of Tissue Engineering, University of Tokyo Hospital, Tokyo 113-8655, Japan
Author contributions: Tsujimura T and Hishikawa K designed and wrote the review; Idei M, Yoshikawa M and Takase O provided critical intellectual input to the study.
Supported by Grants-in-Aid for Young Scientists (B) (No. 15K18454 to Tsujimura T), for Scientific Research (B) (No. 15H03001 to Hishikawa K) and for Scientific Research (C) (Nos. 25461208 to Takase O, 15K09244 to Yoshikawa M and 26462400 to Idei M) from the Japan Society for the Promotion of Science.
Conflict-of-interest statement: All authors declare no conflict-of-interest for this study.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Keiichi Hishikawa, MD, PhD, Department of Advanced Nephrology and Regenerative Medicine, Division of Tissue Engineering, University of Tokyo Hospital, Hongo 7-3-1, Bunkyo-ku, Tokyo 113-8655, Japan. hishikawa-tky@umin.ac.jp
Telephone: +81-3-38155411 Fax: +81-3-58009891
Received: April 27, 2016
Peer-review started: April 28, 2016
First decision: June 16, 2016
Revised: July 12, 2016
Accepted: July 20, 2016
Article in press: July 22, 2016
Published online: September 26, 2016
Processing time: 145 Days and 2.3 Hours
Abstract

The gene encoding bone morphogenetic protein-7 (BMP7) is expressed in the developing kidney in embryos and also in the mature organ in adults. During kidney development, expression of BMP7 is essential to determine the final number of nephrons in and proper size of the organ. The secreted BMP7 acts on the nephron progenitor cells to exert its dual functions: To maintain and expand the progenitor population and to provide them with competence to respond to differentiation cues, each relying on distinct signaling pathways. Intriguingly, in the adult organ, BMP7 has been implicated in protection against and regeneration from injury. Exogenous administration of recombinant BMP7 to animal models of kidney diseases has shown promising effects in counteracting inflammation, apoptosis and fibrosis evoked upon injury. Although the expression pattern of BMP7 has been well described, the mechanisms by which it is regulated have remained elusive and the processes by which the secretion sites of BMP7 impinge upon its functions in kidney development and diseases have not yet been assessed. Understanding the regulatory mechanisms will pave the way towards gaining better insight into the roles of BMP7, and to achieving desired control of the gene expression as a therapeutic strategy for kidney diseases.

Keywords: Bone morphogenetic protein-7; Therapeutics; Kidney; Development; Nephron progenitor cells; Disease; Regeneration; Chromatin conformation; Gene expression; Gene regulation

Core tip: Bone morphogenetic protein-7 (BMP7) plays crucial roles in both the development and regeneration of the kidney. The functions and mechanisms of this protein have been clarified extensively for these processes in the fetus and adult kidney. However, the functional differences of BMP7 secreted from different sites in the kidney remain undefined. We propose that uncovering the regulatory mechanism underlying BMP7 expression will help to solve that issue. Moreover, those data should pave the way towards development of a novel therapeutic strategy for kidney diseases via hyperactivation of the endogenous action of BMP7.