Blog entry by mohammad katout

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Interesting study and exciting results! Tripathi et al. Absence of Canonical Smad Signaling in Ureteral and Bladder Mesenchyme Causes Ureteropelvic Junction Obstruction. J Am Soc Nephrol 2012. doi: 10.1681/ASN.2011060566 The authors unravel the pathogenetic mechanisms at the molecular level resulting in uretero- pelvic junction (UPJ) obstruction, a common congenital anomaly and one of the most common causes of prenatal hydroneonephrosis. The TGF-b superfamily signaling is known to play an important role in normal development of the urogenital system and the pathogenesis of urinary tract defects. Moreover, a number of genes related to TGF-b super family are involved in the pathogenesis of hydronephrosis, including Bmp4, Bmp5, and Id2w. The investigators in the above study reported loss of canonical Smad-dependent TGF-b signaling in the mesenchyme that led to UPJ obstruction and severe hydronephrosis. This initial molecular lesion (deletion of Smad4 in the ureteral mesenchyme) affects the smooth muscle cell number and contractility as well as the urothelial basement membrane at stages before overt urinary tract obstruction. Such earlier deficiencies alter pelviureteric peristalsis, leading to functional obstruction that become more advanced at later stages resulting in organic obstruction, such as the severe kinking of the ureter at the UPJ and the constriction of the ureteral lumen by epithelial crowding. Thus, initial functional obstruction may progress into more damaging and more permanent physical obstruction. Would this discovery open the door in the future to intrauterine interventional targetd correction of the early and usually milder functional alterations before they lead to more irreversible damages to the kidney and the urinary tract? This remains to be answered!
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