**4. Deregulation of the PIWI/piRNA pathway in pathological nonneoplastic disorders**

Mounting evidence has revealed that many transcription factors and signaling molecules interact with the PIWI-piRNA pathway and represent downstream targets of these complexes under pathological conditions. PIWI proteins and piRNAs are deregulated, and their levels of expression are highly altered in various pathological processes. The PIWI-piRNA pathway is pivotal for regeneration after amputation in *Botrylloides leachi* [172]. In Mexican axolotl, PIWIL1 and PIWIL2 transient upregulation in limb blastemal cells induces regeneration of wounded limb [173]. In rat, PIWIL2 expression increases after 24 h of partial hepatectomy, and a set of 72 piR-NAs is deregulated during 48 h of posthepatectomy [58]. In rodents, expression of more than 100 piRNAs is deregulated in brain during ischemic condition [174]. In rat, PIWIL2 enhances activity of the autophagic process in diabetic nephropathy by regulating expression of beclin 1 and LC3A study in diabetic rat kidney [175]. Pro-inflammatory cytokines IL1β and TNFα promote PIWIL2 and PIWIL4 upregulation in synovial fibroblasts of rheumatoid arthritis [176].
