Erythropoietin Accelerates the Regeneration of Ureteral Function in a Murine Model of Obstructive Uropathy

Janßen, Claudia; Jäger, Wolfgang; Moskalev, Igor; Fazli, Ladan; Thüroff, Joachim W.; Lange, Dirk

doi:10.1016/j.juro.2014.08.110

Cited by 8 publications

(10 citation statements)

References 30 publications

(25 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…EPO has previously been demonstrated to improve intestinal dysmotility by increasing the force of contraction in response to acetyl choline administration (15). Our group has shown a similar improvement of ureteral motility following EPO administration in a mouse model of ureteral obstruction (4). In this study using non-obstructed ureteral tissue, we demonstrate that EPO decreases ureteral contraction force in "normal" uninjured human ureteral tissue.…”

Section: Discussionsupporting

confidence: 68%

“…Partial or complete obstruction results in ureteral dysfunction, manifesting as the cessation of peristaltic activity and urine transport from the kidney on the affected side to the bladder. Previous work has shown that the return of peristalsis to pre-obstruction levels is significantly delayed following obstruction reversal and resolution of hydronephrosis, suggesting that negative effects on urine drainage and possibly kidney function are prolonged (4). An improved understanding of mechanisms that drive ureteral peristalsis as well as those elicited by currently used pharmacological approaches to manipulate ureteral function is required for the development of more effective approaches to regulate ureteral peristalsis preand/or post-operatively.…”

Section: Discussionmentioning

confidence: 99%

“…Erythropoietin has been demonstrated to play a role in peristaltic activity of the intestinal smooth muscle (15,16). Erythropoietin receptors are known to populate the kidney (17) and we have recently demonstrated EPO expression in murine ureters (4). While the non-hematopoietic mechanism of action of EPO is currently unclear, we contend that it may work in a similar fashion in ureteral and intestinal smooth muscle cells.…”

Section: Original Articlementioning

confidence: 91%

“…The first protein, the alpha-1 adrenergic receptor (α1-AR) has long been known to play a role in this process however actual mechanistic studies are scarce. Furthermore, studies in our lab and others have suggested a role for erythropoietin (EPO) and Gli proteins in mediating ureteral contractions (4,10,11).…”

Section: Original Articlementioning

confidence: 96%

“…Peristalsis is important in phenomena as varied as stone passage and congenital disorders such as megaureter and ureteropelvic junction obstruction (3). Our group has recently shown that the recovery of ureteral peristalsis following unilateral ureteral obstruction reversal was delayed by 8 days following resolution of hydronephrosis and 11 days following obstruction reversal (4). Given the significant negative effects that disrupted ureteral peristalsis due to obstruction or congenital issues has on kidney function, health and the morbidity of the patient, there exists a need to improve our understanding of the major molecular players in this process to identify potential targets for future therapeutic agents designed to accelerate the recovery of peristalsis following surgical interventions for stones or congenital disorders.…”

Section: Original Articlementioning

confidence: 99%

See 4 more Smart Citations

Mediators of human ureteral smooth muscle contraction—a role for erythropoietin, tamsulosin and Gli effectors

et al. 2021

Self Cite

View full text Add to dashboard Cite

Background: Ureteral contractility is a poorly understood process. Contractions have been demonstrated to occur in the smooth muscle layers of the ureter. Previous work suggests the involvement of Gli family proteins and erythropoietin (EPO) in regulating mammalian ureteral smooth muscle contraction. We sought to devise a method by which the effects of these proteins and tamsulosin on distal human ureteral tissue contractility could be investigated to better understand mechanisms regulating human ureteral function.Methods: IRB approval was obtained to procure portions of extraneous distal ureteral tissue from living donor renal transplants. Contractility was measured by placing the tissue in Krebs buffer and stimulating via a uniform electric current. Contractile force was recorded with each stimulation with and without the presence of a Gli inhibitor (GANT61) or EPO. Each ureteral specimen was subsequently fixed and tested by immunohistochemistry to determine Gli, EPO and alpha-adrenergic receptor activity.Results: Electrical field stimulation successfully elicited contractions in the ureteral tissue. Administering tamsulosin decreased force and duration of ureteral contractions. Inhibiting Gli signaling decreased contractility and EPO decreased ureteral contractile forces within 5 minutes of administration versus untreated controls. Staining confirmed Gli1 protein and α-adrenergic receptor expression in ureteral smooth muscle and epithelial tissue with EPO receptor expression confined to the epithelial layer.Conclusions: Distal ureteral contractile forces are decreased by inhibition of Gli family proteins and the α-adrenergic receptor. EPO acts within five minutes, suggesting ion channel involvement instead of changes in gene expression. Continuing work will elucidate the role of these proteins in coordinating ureteral contractions. This has implications for the use of pharmacologic methods to address ureteral contractility and dysfunctional peristalsis during stone passage, ureteroscopy, in transplant patients and potentially to reduce symptoms from ureteral stents.

show abstract

Section: Discussionsupporting

confidence: 68%

Section: Discussionmentioning

confidence: 99%