BERKELEY, CA (UroToday.com) -
Stromal Induction and Renal Pelviceal Squamous Metaplasia
In our recent paper, we suggested (in the discussion section) that factors in the underlying renal pelviceal stroma may have played a role in the abrupt transition to metaplastic differentiation at the junction of the major and minor calyces.
The concept of stromal induction is well documented in renal embryogensis. For example, renal morphogensis is initiated when metanephric mesenchyme is invaded by the uretric bud. The two structures then synergistically release paracrine factors that support growth, differentiation, and epithelization of the nephrons and associated renal collection systems, respectively. Metanephric mesenchyme differentiates into additional cell types, including stromal cells (distinct from those responsible for forming nephrons or the collecting duct system). The function and importance of the stroma for renal morphogensis has recently been better elucidated. Using strains of “knock-out” mice, recent studies have identified two transcription factors (RAR and BF-2) native to the renal stroma that, when deleted, interfered with the differentiation and development of the collecting duct system. This supports the role of stromal signaling of nearby developing tissue to promote differentiation into various cell types. It is these signaling systems that we believe may be responsible for the cases of squamous metaplasia in KDSM that lack an associated inciting injury or chronic inflammatory state.
The abrupt transition from metaplastic squamous epithelium to the native low cuboidal urothelium of the minor calyces in our case description may offer some insight into the mechanism of KDSM. We postulate that the underlying ureteral smooth muscle or its autonomic innervation (absent in the renal parenchyma) may provide either a biological impetus for paracrine factors that support metaplasia in the overlying mucosal surface, or in the absence of either smooth muscle or autonomic innervation, a means of limiting the development of metaplastic changes. In our observations, there is often an association between squamous metaplasia and smooth muscle in other tissue types. It is possible that this symbiosis is driven by an epithilum smooth-muscle relationship not yet well understood.
Alternatively, the presence of either more prominent vascular components in the renal parenchyma of the minor calyces or an enhanced stromal response to factors promoting angiogenesis may provide a less hypoxic stromal milieu (or decreased accumulation of paracrine factors) that may serve to limit metaplastic differentiation in the overlying epithelial surfaces.
In either case, the mechanisms underlying squamous metaplasia offer opportunities to further elucidate these mechanisms in renal disease.
Written by:
Richard H. Siderits, MDa and Noah S. Rolleri, MS-IVb as part of Beyond the Abstract on UroToday.com. This initiative offers a method of publishing for the professional urology community. Authors are given an opportunity to expand on the circumstances, limitations etc... of their research by referencing the published abstract.
a Department of Pathology
Robert Wood Johnson University Hospital
Hamilton, NJ 08690-3599 USA
b Robert Wood Johnson Medical School
Renal pelviceal keratinizing squamous metaplasia with sparing of pyramidal zones - Abstract
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