Renal autocrine and paracrine signaling -a story of self-protection.

Autocrine and paracrine signaling in the kidney adds an extra level of diversity and complexity to renal physiology. The extensive scientific production on the topic precludes easy understanding of the fundamental purpose of the vast number of molecules and systems that influence the renal function. This systematic review provides the broader pen strokes for a collected image of renal paracrine signaling. First, we recapitulate the essence of each paracrine system one by one. Thereafter the single components are merged into an overarching physiological concept. The presented survey shows that despite the diversity in the web of paracrine factors, the collected effect on renal function may not be complicated after all. In essence, paracrine activation provides an intelligent system that perceives minor perturbations and reacts with a coordinated and integrated tissue response that relieves the workload from the renal epithelia and favors diuresis and natriuresis. We suggest that the overall function of paracrine signaling is reno-protection and argue that renal paracrine signaling and self-regulation are two sides of the same coin. Thus, local paracrine signaling is an intrinsic function of the kidney, and the overall renal effect of changes in blood pressure, volume load, and systemic hormones will always be tinted by its paracrine status.